Hereditary sensory and autonomic neuropathy type III (HSAN III, Riley–Day syndrome, Familial Dysautomia) is characterised by elevated thermal thresholds and an indifference to pain. Using microelectrode recordings we recently showed that these patients possess no functional stretch-sensitive mechanoreceptors in their muscles (muscle spindles), a feature that may explain their lack of stretch reflexes and ataxic gait, yet patients have apparently normal low-threshold cutaneous mechanoreceptors. The density of C-fibres in the skin is markedly reduced in patients with HSAN III, but it is not known whether the C-tactile afferents, a distinct type of low-threshold C fibre present in hairy skin that is sensitive to gentle stroking and has been implicated in the coding of pleasant touch are specifically affected in HSAN III patients. We addressed the relationship between C-tactile afferent function and pleasant touch perception in 15 patients with HSAN III and 15 age-matched control subjects. A soft make-up brush was used to apply stroking stimuli to the forearm and lateral aspect of the leg at five velocities: 0.3, 1, 3, 10 and 30 cm/s. As demonstrated previously, the control subjects rated the slowest and highest velocities as less pleasant than those applied at 1–10 cm/s, which fits with the optimal velocities for exciting C-tactile afferents. Conversely, for the patients, ratings of pleasantness did not fit the profile for C-tactile afferents. Patients either rated the higher velocities as more pleasant than the slow velocities, with the slowest velocities being rated unpleasant, or rated all velocities equally pleasant. We interpret this to reflect absent or reduced C-tactile afferent density in the skin of patients with HSAN III, who are likely using tactile cues (i.e. myelinated afferents) to rate pleasantness of stroking or are attributing pleasantness to this type of stimulus irrespective of velocity.
•C-tactile afferents in hairy skin are believed to mediate affective touch.•They are sensitive to slow brushing stimuli, which are perceived as pleasant.•It is not known whether C-tactile afferents are affected in HSAN III.•Ratings of pleasantness were reduced in 15 HSAN III patients compared to controls.•We suggest that the density of C-tactile afferents is reduced in HSAN III.
Affective touch; CT afferents; Pleasant touch; Tactile sensation
Peripheral neuropathies are a heterogeneous group of diseases affecting peripheral nerves. The causes are multiple: hereditary, metabolic, infectious, inflammatory, toxic, traumatic. The temporal profile includes acute, subacute and chronic conditions. The majority of peripheral neuropathies cause mainly muscle weakness and sensory loss, positive sensory symptoms and sometimes pain. When pain is present, however, it is usually extremely intense and among the most disabling symptoms for the patients. In addition, the neurological origin of the pain is often missed and patients receive inadequate or delayed specific treatment. Independently of the disease causing the peripheral nerve injury, pain originating from axonal pathology or ganglionopathy privileges neuropathies affecting smaller fibres, a clinical observation that points towards abnormal activity within nociceptive afferents as a main generator of pain. Natural activation of blood vessels or perineurial nociceptive network by pathology also causes intense pain. Pain of this kind, i.e. nerve trunk pain, is among the heralding symptoms of inflammatory or ischemic mononeuropathy and for its intensity represents itself a medical emergency. Neuropathic pain quality rekindles the psychophysical experience of peripheral nerves intraneural microstimulation i.e. a combination of large and small fibres sensation temporally distorted compared to physiological perception evoked by natural stimuli. Pins and needles, burning, cramping mixed with numbness, and tingling are the wording most used by patients. Nociceptive pain instead is most often described as aching, deep and dull. Good command of peripheral nerve anatomy and pathophysiology allows timely recognition of the different pain components and targeted treatment, selected according to intensity, type and temporal profile of the pain.
Pain; neuropathic; polyneuropathy; small fibres neuropathy; diabetic neuropathy; post herpetic neuralgia; paraneoplastic polyneuropathy; hereditary neuropathy
Hereditary sensory and autonomic neuropathy type III features a marked ataxic gait that progressively worsens over time. We assessed whether proprioceptive disturbances can explain the ataxia. Proprioception at the knee joint was assessed using passive joint angle matching in 18 patients and 14 age-matched controls; 5 patients with cerebellar ataxia were also studied. Ataxia was quantified using the Brief Ataxia Rating Score, which ranged from 7 to 26/30. Neuropathy patients performed poorly in judging joint position: mean absolute error was 8.7±1.0° and the range was very wide (2.8–18.1°); conversely, absolute error was only 2.7±0.3° (1.6–5.5°) in the controls and 3.0±0.2° (2.1–3.4°) in the cerebellar patients. This error was positively correlated to the degree of ataxia in the neuropathy patients but not the cerebellar patients, suggesting that poor proprioceptive acuity at the knee joint is a major contributor to the ataxic gait associated with hereditary sensory and autonomic neuropathy type III.
congenital insensitivity to pain; familial dysautonomia; joint sense; hereditary sensory & autonomic neuropathy; muscle spindles; proprioception; Riley-Day syndrome
The hereditary sensory and autonomic neuropathies (HSAN) encompass a number of inherited disorders that are associated with sensory dysfunction (depressed reflexes, altered pain and temperature perception) and varying degrees of autonomic dysfunction (gastroesophageal reflux, postural hypotention, excessive sweating). Subsequent to the numerical classification of four distinct forms of HSAN that was proposed by Dyck and Ohta, additional entities continue to be described, so that identification and classification are ongoing. As a group, the HSAN are rare diseases that affect both sexes. HSAN III is almost exclusive to individuals of Eastern European Jewish extraction, with incidence of 1 per 3600 live births. Several hundred cases with HSAN IV have been reported. The worldwide prevalence of HSAN type II is very low. This review focuses on the description of three of the disorders, HSAN II through IV, that are characterized by autosomal recessive inheritance and onset at birth. These three forms of HSAN have been the most intensively studied, especially familial dysautonomia (Riley-Day syndrome or HSAN III), which is often used as a prototype for comparison to the other HSAN. Each HSAN disorder is likely caused by different genetic errors that affect specific aspects of small fiber neurodevelopment, which result in variable phenotypic expression. As genetic tests are routinely used for diagnostic confirmation of HSAN III only, other means of differentiating between the disorders is necessary. Diagnosis is based on the clinical features, the degree of both sensory and autonomic dysfunction, and biochemical evaluations, with pathologic examinations serving to further confirm differences. Treatments for all these disorders are supportive.
OBJECTIVE—To develop a
method for the detection of bilateral Horner's syndrome in patients
with bilateral interruption of the cervical sympathetic pathway or
widespread autonomic neuropathy.
pupil diameters and redilatation times during light reflexes have been
recorded with infrared TV pupillometry in 65 healthy subjects, 47 patients with unilateral Horner's syndrome, and 20 patients with
bilateral Horner's syndrome. The aetiologies of the last group were
diabetic autonomic neuropathy (three cases), amyloidosis (four), pure
autonomic failure (PAF) (four), dopamine-β-hydroxylase deficiency
(two), and one case each of hereditary sensory and autonomic neuropathy
(HSAN) type III, carcinomatous sympathetic neuropathy, familial
dysautonomia, multiple system atrophy, Anderson-Fabry disease, and
anterior spinal artery thrombosis at C5,6 and one had had bilateral
diameters on the affected side were below normal in 12 patients with
unilateral Horner's syndrome, the measurement yielding only 26%
sensitivity for detection of the condition. By contrast, the time taken
to reach three quarter recovery in the light reflex (T3/4)
was abnormally prolonged (redilatation lag) in 33 of the same eyes. The
measurement yielded 70% sensitivity and 95% specificity for detection
of the condition. In 20 cases, diagnosed on clinical grounds as having
bilateral Horner's syndrome of various aetiologies, pupil diameters
were abnormally small on both sides in five and on one side in three
patients. Fourteen of these patients had significant redilatation lag
in both eyes, five patients in one eye, and one patient had it in
neither eye. Measurement of redilatation lag was therefore a more
sensitive diagnostic test than pupil diameter in both unilateral and
bilateral Horner's syndrome.
that the pupils are not tonic, bilateral Horner's syndrome can be
diagnosed on the basis of redilatation lag. It occurs clinically in
some generalised autonomic neuropathies and with interruption of the
local sympathetic nerve supplies to the two eyes.
Peripheral neuropathy refers to disorders of the peripheral nervous system. They have numerous causes and diverse presentations; hence, a systematic and logical approach is needed for cost-effective diagnosis, especially of treatable neuropathies. A detailed history of symptoms, family and occupational history should be obtained. General and systemic examinations provide valuable clues. Neurological examinations investigating sensory, motor and autonomic signs help to define the topography and nature of neuropathy. Large fiber neuropathy manifests with the loss of joint position and vibration sense and sensory ataxia, whereas small fiber neuropathy manifests with the impairment of pain, temperature and autonomic functions. Electrodiagnostic (EDx) tests include sensory, motor nerve conduction, F response, H reflex and needle electromyography (EMG). EDx helps in documenting the extent of sensory motor deficits, categorizing demyelinating (prolonged terminal latency, slowing of nerve conduction velocity, dispersion and conduction block) and axonal (marginal slowing of nerve conduction and small compound muscle or sensory action potential and dennervation on EMG). Uniform demyelinating features are suggestive of hereditary demyelination, whereas difference between nerves and segments of the same nerve favor acquired demyelination. Finally, neuropathy is classified into mononeuropathy commonly due to entrapment or trauma; mononeuropathy multiplex commonly due to leprosy and vasculitis; and polyneuropathy due to systemic, metabolic or toxic etiology. Laboratory investigations are carried out as indicated and specialized tests such as biochemical, immunological, genetic studies, cerebrospinal fluid (CSF) examination and nerve biopsy are carried out in selected patients. Approximately 20% patients with neuropathy remain undiagnosed but the prognosis is not bad in them.
Axonal demyelination; diagnosis; nerve conduction; peripheral neuropathy
To determine whether central nervous conduction deficits are related to the degree of peripheral neuropathy somatosensory evoked potentials (SEP) were measured after tibial nerve stimulation in 51 healthy subjects aged 39.3 (SE 2.0, (range 21-71) years and 100 insulin dependent diabetic patients aged 37.3 (1.5, 18-73) years. Five criteria were used for staging of peripheral neuropathy: nerve conduction; thermal discrimination threshold; vibration perception threshold; tendon reflexes; and neuropathic symptoms. Thirty seven patients had fewer than two abnormalities among the first four criteria and no symptoms (stage 0 = no neuropathy), 37 had 2 or more abnormalities but no symptoms (stage 1 = subclinical neuropathy); 26 had 2 or more abnormalities in conjunction with symptoms (stage 2 = symptomatic neuropathy). Multiple regression analysis was used to define the age and height dependent limits of normal of SEP at the 97.5th and 2.5th centiles. In five patients with stage 1, seven patients with stage 2, but no patient with stage 0 the individual SEP components were unrecordable. The relative frequencies of abnormally prolonged or non-evokable popliteal N8 latency as well as cortical N33 latency and N33/P40 amplitude increased significantly from stage 0 (3-30%) to stage 1 (22-62%) and stage 2 (46-84%) (p < 0.05 for each component and stage). The numbers and percentages of abnormal recordable spinal N22-30 and supraspinal N30-33 interpeak latencies were two (6.3%) and four (11.8%) in patients with stage 0, but these rates did not increase in subjects with stage 1 or 2. The components of SEP were significantly associated with the indices of peripheral and autonomic function tests. There were no major relations between the latencies of SEP and duration of diabetes or prevailing glycaemic control. These findings suggest that the degree of dysfunction along the somatosensory afferent pathways in insulin dependent diabetic patients depends on the stage of peripheral neuropathy; is not related to the degree of glycaemic control or duration of diabetes; and can be characterized mainly by an alteration of the cortical sensory complex and peripheral transmission delay, while spinal and supraspinal conduction deficits are detected infrequently.
Spinal manipulation (SM) is a form of manual therapy used clinically to treat patients with low back and neck pain. The most common form of this maneuver is characterized as a high velocity (duration < 150ms), low amplitude (segmental translation < 2mm, rotation < 4°, and applied force 220-889N) impulse thrust (HVLA-SM). Clinical skill in applying an HVLA-SM lies in the practitioner's ability to control the duration and magnitude of the load (i.e., the rate of loading), the direction in which the load is applied, and the contact point at which the load is applied. Control over its mechanical delivery presumably related to its clinical effects. Biomechanical changes evoked by an HVLA-SM are thought to have physiological consequences caused, at least in part, by changes in sensory signaling from paraspinal tissues.
If activation of afferent pathways does contribute to the effects of an HVLA-SM, it seems reasonable to anticipate that neural discharge might increase or decrease in a non-linear fashion as the thrust duration thrust approaches a threshold value. We hypothesized that the relationship between the duration of an impulsive thrust to a vertebra and paraspinal muscle spindle discharge would be non-linear with an inflection near the duration of an HVLA-SM delivered clinically (<150ms). In addition, we anticipated that muscle spindle discharge would be more sensitive to larger amplitude thrusts.
A neurophysiological study of spinal manipulation using the lumbar spine of a feline model.
Impulse thrusts (duration: 12.5, 25, 50, 100, 200, and 400 ms; amplitude 1 or 2mm posterior to anterior) were applied to the spinous process of the L6 vertebra of deeply anesthetized cats while recording single unit activity from dorsal root filaments of muscle spindle afferents innervating the lumbar paraspinal muscles. A feedback motor was used in displacement control mode to deliver the impulse thrusts. The motor's drive arm was securely attached to the L6 spinous process via a forceps.
As thrust duration became shorter the discharge of the lumbar paraspinal muscle spindles increased in a curvilinear fashion. A concave up inflection occurred near the 100ms duration eliciting both a higher frequency discharge compared to the longer durations and a substantially faster rate of change as thrust duration was shortened. This pattern was evident in paraspinal afferents with receptive fields both close and far from the midline. Paradoxically, spindle afferents were almost twice as sensitive to the 1mm compared to the 2mm amplitude thrust (6.2 vs 3.3 spikes/s/mm/s). This latter finding may be related to the small vs large signal range properties of muscle spindles.
. The results indicate that the duration and amplitude of a spinal manipulation elicits a pattern of discharge from paraspinal muscle spindles different from slower mechanical inputs. Clinically, these parameters may be important determinants of an HVLA-SM's therapeutic benefit.
lumbar spine; spinal manipulation; chiropractic; osteopathy; paraspinal muscles; muscle spindle
Five members of a single family presented with neuropathic deformities and ulceration of the feet developing in the first and second decades of life, and progressed slowly over many years. In this form of hereditary sensory and autonomic neuropathy, there was minimal tendon reflex impairment, cutaneous sensory impairment was restricted to the feet, and there was no autonomic dysfunction. The only neurophysiological abnormality was that of reduced or absent sural nerve sensory action potentials. Sural nerve biopsies taken from two affected family members showed changes of a chronic neuropathy with loss of myelinated fibres, particularly affecting those of small diameter. Unmyelinated fibres were present in normal numbers. This condition differed from other forms of hereditary sensory and autonomic neuropathy having an X-linked recessive mode of inheritance.
Congenital insensitivity to pain with anhidrosis, also known as hereditary sensory and autonomic neuropathy type IV, is an autosomal recessive disorder characterized by the congenital lack of pain sensation, inability to sweat, episodes of recurrent hyperpyrexia, mental retardation, and self-mutilating behavior. It is an extremely rare disorder with only a handful of reports from India. A five- year- old boy, born to second-degree consanguineous parents after uneventful antenatal period, presented to us with history of recurrent unexplained fever, recurrent ulcers in the lower limbs, insensitivity to painful stimuli (like injections, vaccination) and self-mutilating behavior from early childhood. Cutaneous examination showed multiple ulcers, loss of teeth, loss of tip of the tongue (due to biting), scarring of finger tips, xerosis and lichenification. Sensory examination showed complete loss of pain and temperature sensations, but fine touch and vibration were preserved. Deep tendon reflexes were normal. Evaluation for Hansen's disease was non-contributory. An intradermal injection of histamine did not show any flare response. Based on clinical as well as compatible histological features a diagnosis of congenital insensitivity to pain with anhidrosis was made. The ulcers were treated with appropriate antibiotics and daily dressings. The parents were counseled about appropriate care of the child.
Congenital insensitivity to pain with anhidrosis; hereditary sensory and autonomic neuropathy type IV; self-mutilation
Twenty-eight mechanoreceptive units identified as primary or secondary spindle afferents were sampled from muscle nerve fascicles in the median, peroneal, and tibial nerves of healthy adult subjects. The responses of these units to sustained passive muscle stretch, to passive stretching movements, to tendon taps, and electrically-induced muscle twitches were studied while the subject performed repeated Jendrassik manoeuvres involving strong voluntary contractions in distant muscle groups. The manoeuvres had no effect upon the afferent spindle discharges as long as there were no EMG signs of unintentional contractions occurring in the receptor-bearing muscle and no mechanotransducer signs of unintentional positional changes altering the load on that muscle. Unintentional contractions in the receptor-bearing muscle frequently occurred during the manoeuvres, however, and then coactivation of the spindle afferents was observed. Multiunit afferent responses to Achilles tendon taps, led off from tibial nerve fascicles, were in a similar way uninfluenced by the Jendrassik manoeuvres, even when these resulted in marked reinforcement of the calf muscle tendon jerk. The results provide no evidence for fusimotor sensitization of spindles in muscles remaining relaxed during the Jendrassik manoeuvre, and reflex reinforcement occurring without concomitant signs of active tension rise in the muscles tested is presumed to depend upon altered processing of the afferent volleys within the cord.
Classic chronic inflammatory demyelinating polyneuropathy (CIDP), an acquired demyelination of peripheral nerves and nerve roots presents with symmetric motor and sensory involvement, weakness in proximal and distal muscles, globally diminished or absent reflexes, painful dysesthesias, and back pain with no brain involvement. In this case, a highly functional lawyer presents with reversible dementia and motor and sensory symptoms consistent with CIDP. This case may represent a new clinical entity of CIDP with reversible dementia.
A 60-year-old man presented with progressive weakness, and cognitive dysfunction in the form of dementia over the last 8 weeks. Sensory and motor weakness continued to progress affecting upper and lower extremities with both proximal and distal muscle groups to the point where the patient was unable to move without assistance. The patient had word finding difficulty, short-term memory impairment, and was disoriented, despite his comprehension being intact. Initial Montreal Cognitive Assessment (MoCA) was 12/30. Initial neurologic exam was notable for muscle strength 3/5, globally depressed deep tendon reflexes. Lumbar puncture revealed elevated protein with no pleocytosis and no serum paraprotein. EMG/NCS demonstrated mixed sensorimotor axonal and demyelination peripheral polyneuropathy. CIDP was diagnosed based on clinical history according to Koski criteria. He was started on a 5-day treatment of IVIG, after which he had marked cognitive improvement after just one dose and improvement in weakness after the second dose of IVIG. Three weeks after IVIG treatment, the patient's cognitive function was back at baseline with MoCA score 29/30; no further word finding difficulty, and no short term memory impairment. At discharge, the patient's weakness had significantly improved to the point where he was able to walk with only the aid of a walker. His neurologic exam had improved as well as his muscle strength 4/5 and 2/4 deep tendon reflexes. Left sural nerve biopsy would eventually reveal moderate peripheral neuropathy with axonal degeneration, moderate loss of large and small myelinated nerve fibers, confirming diagnosis of CIDP.
CIDP encompasses several different variants, including Lewis-Sumner syndrome, distal acquired demyelinating sensory neuropathy, sensory predominant CIDP among other variants. However, none of the variations of CIDP have a reversible cognitive impairment component. Patient met diagnosis of CIDP according to Koski criteria, as he had chronic polyneuropathy progressive for at least 8 weeks with no serum paraprotein, no genetic abnormality, and symmetric exam revealing weakness in all four limbs and proximal weakness in both lower extremities. Potentially, the patient could have had simultaneous diagnosis of dementia and CIDP, but the marked improvement in cognitive function after just one dose of IVIG makes that theory unlikely. PubMed search yielded no single case of CIDP with supratentorial manifestations in a patient with normal brain MRI. This case may represent a new clinical variant: CIDP with cognitive impairment.
Hereditary sensory neuropathy type I (HSN I) is a slowly progressive neurological disorder characterised by prominent predominantly distal sensory loss, autonomic disturbances, autosomal dominant inheritance, and juvenile or adulthood disease onset. The exact prevalence is unknown, but is estimated as very low. Disease onset varies between the 2nd and 5th decade of life. The main clinical feature of HSN I is the reduction of sensation sense mainly distributed to the distal parts of the upper and lower limbs. Variable distal muscle weakness and wasting, and chronic skin ulcers are characteristic. Autonomic features (usually sweating disturbances) are invariably observed. Serious and common complications are spontaneous fractures, osteomyelitis and necrosis, as well as neuropathic arthropathy which may even necessitate amputations. Some patients suffer from severe pain attacks. Hypacusis or deafness, or cough and gastrooesophageal reflux have been observed in rare cases. HSN I is a genetically heterogenous condition with three loci and mutations in two genes (SPTLC1 and RAB7) identified so far. Diagnosis is based on the clinical observation and is supported by a family history. Nerve conduction studies confirm a sensory and motor neuropathy predominantly affecting the lower limbs. Radiological studies, including magnetic resonance imaging, are useful when bone infections or necrosis are suspected. Definitive diagnosis is based on the detection of mutations by direct sequencing of the SPTLC1 and RAB7 genes. Correct clinical assessment and genetic confirmation of the diagnosis are important for appropriate genetic counselling and prognosis. Differential diagnosis includes the other hereditary sensory and autonomic neuropathies (HSAN), especially HSAN II, as well as diabetic foot syndrome, alcoholic neuropathy, neuropathies caused by other neurotoxins/drugs, immune mediated neuropathy, amyloidosis, spinal cord diseases, tabes dorsalis, lepra neuropathy, or decaying skin tumours like amelanotic melanoma. Management of HSN I follows the guidelines given for diabetic foot care (removal of pressure to the ulcer and eradication of infection, followed by the use of specific protective footwear) and starts with early and accurate counselling of patients about risk factors for developing foot ulcerations. The disorder is slowly progressive and does not influence life expectancy but is often severely disabling after a long duration of the disease.
Congenital insensitivity to pain and anhidrosis (CIPA) or hereditary sensory autonomic neuropathies type IV (HSAN type IV) is an extremely rare autosomal recessive disorder initially described by Swanson in 1963.
We report a 2.5-year-old boy with clinical features of CIPA as the first case in Iran. The symptoms included recurrent episodes of hyperthermia and unexplained fever that began in early infancy, anhidrosis (inability to sweat), profound loss of pain sensitivity, neurodevelopmental delay, unconscious self-mutilation of fingers, lips and tongue, corneal lacerations, palmar hyperkeratosis, non-painful fracture and joint deformities in the right ankle. Tearing, deep tendon reflexes and motor and sensory nerve action potentials were normal.
Prenatal screening is the sole accessible option to prevent the birth of an affected child as no cure is available. Early recognition of CIPA patients and its orthopedic complications, prevention of accidental injuries, regular visual and eye follow-up and specific dental management could be useful in the reduction of frequency and severity of complications.
HSAN type IV; Congenital insensitivity to pain; Anhidrosis
Spinal integration of sensory signals associated with hip position, muscle loading, and cutaneous sensation of the foot contributes to movement regulation. The exact interactive effects of these sensory signals under controlled dynamic conditions are unknown. The purpose of the present study was to establish the effects of combined plantar cutaneous afferent excitation and hip movement on the Hoffmann (H) and flexion reflexes in people with a spinal cord injury (SCI). The flexion and H-reflexes were elicited through stimulation of the right sural (at non-nociceptive levels) and posterior tibial nerves respectively. Reflex responses were recorded from the ipsilateral tibialis anterior (TA) (flexion reflex) and soleus (H-reflex) muscles. The plantar cutaneous afferents were stimulated at three times the perceptual threshold (200 Hz, 24-ms pulse train) at conditioning–test intervals that ranged from 3 to 90 ms. Sinusoidal movements were imposed to the right hip joint at 0.2 Hz with subjects supine. Control and conditioned reflexes were recorded as the hip moved in flexion and extension. Leg muscle activity and sagittal-plane joint torques were recorded. We found that excitation of plantar cutaneous afferents facilitated the soleus H-reflex and the long latency flexion reflex during hip extension. In contrast, the short latency flexion reflex was depressed by plantar cutaneous stimulation during hip flexion. Oscillatory joint forces were present during the transition phase of the hip movement from flexion to extension when stimuli were delivered during hip flexion. Hip-mediated input interacts with feedback from the foot sole to facilitate extensor and flexor reflex activity during the extension phase of movement. The interactive effects of these sensory signals may be a feature of impaired gait, but when they are appropriately excited, they may contribute to locomotion recovery in these patients.
H-reflex; Flexion reflex; Locomotion; Reflex circuits; Rehabilitation; Sensorimotor integration
patients were studied to understand whether stance unsteadiness is
associated with changes in the control of voluntary force, muscle tone,
or reflex excitability, rather than to abnormal posture connected to
the motor deficit itself.
normal subjects, 12 patients affected by amyotrophic lateral sclerosis
(ALS), seven by spastic paraparesis, and 14 by hemiparesis were
studied. All patients featured various degrees of spasticity and
paresis but were free from clinically evident sensory deficits. Body
sway during quiet upright stance was assessed through a stabilometric
platform under both eyes open (EO) and eyes closed (EC) conditions. The
sudden rotation of a supporting platform, in a toe up and toe down
direction respectively, evoked short (SLR) and medium latency (MLR)
reflex responses to stretch of the soleus or the tibialis anterior (TA) muscle.
was found between clinical findings (tone, muscle strength, tendon
reflexes, plantar response, and duration of disease) and body sway. On
average, all patient groups exhibited a forward shift of the centre of
foot pressure (CFP) with respect to normal subjects; in addition,
paraparetic and to a much larger extent hemiparetic patients showed a
lateral shift of CFP. Body sway area was significantly increased only
in the hemiparetic patients. No relation was found between position of
the CFP and sway within any patient group. Soleus SLR was increased in
all patients with respect to normal subjects. TA SLR was often seen in
both patients with ALS and paraparetic patients, but only rarely in
normal subjects and hemiparetic patients. However, no relation was
found between amplitude of soleus or TA SLRs and stabilometric variables. The frequency and size of soleus MLR and TA MLR were decreased in all patients. These responses were decreased in size and
not modulated by background EMG in the affected leg of hemiparetic patients, suggesting a disturbed control of spinal reflexes fed by
spindle group II afferent fibres.
proposed that body posture, paresis, or monosynaptic reflex
hyperexcitability do not affect the control of equilibrium during quiet
upright stance. In hemiparetic patients, the decreased amplitude of
MLRs might be the main cause of the large postural instability. The
results are congruent with the hypothesis of a role for group II
afferent input in the reflex control of equilibrium.
Objective: To investigate a comprehensive battery of neurophysiological tests for objective evaluation of sensory neuropathies including fibre type involvement and severity, and to determine the relation between neurophysiological data and clinical examination.
Methods: 45 patients referred for sensory neuropathy were studied using a standardised clinical evaluation of large and small fibre symptoms and an original neurophysiological battery. Clinical evaluation included: assessment of tactile, vibratory, and pin sensation; tendon reflexes; toe position sense; ataxia score; pain level; and presence of trophic, vasomotor, or sudomotor abnormalities. The neurophysiological battery included: recording of large fibre and small fibre components of the sural sensory nerve action potential; somatosensory evoked cortical potentials and soleus H reflex following tibial nerve electrical stimulation; laser evoked potentials following Nd:YAG laser stimulation of the foot; and plantar sympathetic skin response to median nerve stimulation. Neuropathy was classified according to the predominantly affected fibre type, and a severity score was established based on clinical and neurophysiological abnormalities.
Results: On clinical examination there were 22 patients with large fibre sensory neuropathy (LFSN), 18 with mixed sensory neuropathy (MSN), and five with small fibre sensory neuropathy (SFSN). Neurophysiological classification identified 25 patients with LFSN, 13 with MSN, and seven with SFSN. Clinical and neurophysiological classifications and severity scores were correlated, whatever the type of neuropathy.
Conclusions: The correlation between clinical examination and the results of an original neurophysiological test battery offers a comprehensive clinical and neurophysiological approach to the objective assessment of peripheral neuropathies according to fibre type involvement and overall severity.
The experiments reported in this paper tested the hypothesis that the afferent potential elicited by a tendon tap in an isometrically recorded phasic stretch reflex can be detected in the surface EMG of normal humans when appropriate techniques are used. These techniques involved (1) training the subjects to relax mentally and physically so that the EMG was silent before and immediately after the diphasic MAP which reflects a highly synchronous discharge of afferent impulses from low threshold muscle stretch receptors after a tendon tap, and (2) using a data retrieval computer to summate stimulus-locked potentials in the EMG over a series of 16 samples using taps of uniform peak force and duration on the Achilles tendon to elicit the tendon jerk in the calf muscles. A discrete, diphasic potential (`A-wave') was recorded from EMG electrodes placed on the surface of the skin over the medial gastrocnemius muscle. The `A-wave' afferent potential had the opposite polarity to the corresponding efferent MAP. Under control conditions of relaxation the `A-wave' had a latency after the onset of the tap of 2 msec, the peak to peak amplitude was of the order of 5 μV and the duration was in the range of 6 to 10 msec. Further experiments were conducted to show that the `A-wave' (1) was not an artefact of the instrumentation used, (2) had a threshold at low intensities of stimulation, and (3) could be reliably augmented by using a Jendrassik manoeuvre compared with the potential observed during control (relaxation) conditions. The results support the conclusion that the `A-wave' emanates from the pool of muscle spindles which discharges impulses along group Ia nerve fibres in response to the phasic stretch stimulus because the primary ending of the spindles is known to initiate the stretch reflex and the spindles can be sensitized by fusimotor impulses so that their threshold is lowered as a result of a Jendrassik manoeuvre. The finding has important implications for the investigation of the fusimotor system in intact man.
Pathological expression of movement and muscle tone in human upper motor neuron disorders has been partly associated with impaired modulation of spinal inhibitory mechanisms, such as reciprocal or presynaptic inhibition. In addition, input from specific afferent systems contributes significantly to spinal reflex circuits coupled with posture or locomotion. Accordingly, the objectives of this study were to identify the involved afferents and their relative contribution to soleus H-reflex modulation induced by changes in hip position, and to relate these effects with activity of spinal interneuronal circuits. Specifically, we investigated the actions of group I synergistic and antagonistic muscle afferents (e.g. common peroneal nerve, CPN; medial gastrocnemius, MG) and tactile plantar cutaneous afferents on the soleus H-reflex during controlled hip angle variations in 11 motor incomplete spinal cord injured (SCI) subjects. It has been postulated in healthy subjects that CPN stimulation evokes an inhibition on the soleus H-reflex at a conditioning test (C-T) interval of 2–4 ms. This short latency reflex depression is caused mainly by activation of the reciprocal Ia inhibitory pathway. At longer C-T intervals (beyond 30 ms) the soleus H-reflex is again depressed, and is generally accepted to be caused by presynaptic inhibition of soleus Ia afferents. Similarly, MG nerve stimulation depresses soleus H-reflex excitability at the C-T interval of 6 ms, involving the pathway of non-reciprocal group I inhibition, while excitation of plantar cutaneous afferents affects the activity of spinal reflex pathways in the extensors. In this study, soleus H-reflexes recorded alone or during CPN stimulation at either short (2, 3, 4 ms) or long (80, 100, 120 ms) C-T intervals, and MG nerve stimulation delivered at 6 ms were elicited via conventional methods and similar to those adopted in studies conducted in healthy subjects. Plantar skin conditioning stimulation was delivered through two surface electrodes placed on the metatarsals at different C-T intervals ranging from 3 to 90 ms. CPN stimulation at either short or long C-T intervals and MG nerve stimulation resulted in a significant facilitation of the soleus H-reflex, regardless of the hip angle tested. Plantar skin stimulation delivered with hip extended at 10° induced a bimodal facilitation reflex pattern, while with hip flexed (10°, 30°) the reflex facilitation increased with increments in the C-T interval. This study provides evidence that in human chronic SCI, classically key inhibitory reflex actions are switched to facilitatory, and that spinal processing of plantar cutaneous sensory input and actions of synergistic/antagonistic muscle afferents interact with hip proprioceptive input to facilitate soleus H-reflex excitability. These actions might be associated with the pathological expression of neural control of movement in individuals with SCI, and potentially could be considered in rehabilitation programs geared to restore sensorimotor function in these patients.
H-reflex; Hip; Cutaneous afferents; Postsynaptic/presynaptic inhibition; Rehabilitation
Muscle spindles provide proprioceptive feedback supporting normal patterns of motor activity and kinesthetic sensibility. During mastication, jaw muscle spindles play an important role in monitoring and regulating the chewing cycle and the bite forces generated during mastication. Both acute and chronic orofacial pain disorders are associated with changes in proprioceptive feedback and motor function. Experimental jaw muscle pain also alters the normal response of masseter spindle afferents to ramp and hold jaw movements . It has been proposed that altered motor function and proprioceptive input results from group III muscle afferent modulation of the fusimotor system which alters spindle afferent sensitivity in limb muscles. The response to nociceptive stimuli may enhance or reduce the response of spindle afferents to proprioceptive stimuli. Several experimental observations suggesting the possibility that a similar mechanism also functions in jaw muscles are presented in this report. First, evidence is provided to show that nociceptive stimulation of the masseter muscle primarily influences the amplitude sensitivity of spindle afferents with relatively little effect on the dynamic sensitivity . Second, reversible inactivation of the caudal trigeminal nuclei attenuates the nociceptive modulation of spindle afferents. Finally, functionally identified gamma-motoneurons in the trigeminal motor nucleus are modulated by intramuscular injection with algesic substances. Taken together, these results suggest that pain-induced modulation of spindle afferent responses are mediated by small diameter muscle afferents and that this modulation is dependent, in part, on the relay of muscle nociceptive information from trigeminal subnucleus caudalis onto trigeminal gamma-motoneurons. The implication of these results will be considered in light of current theories on the relationship between jaw muscle pain and oral motor function.
Muscle spindle afferents; Masseter muscle; Pain; Proprioception; Rats
ABSTRACT Twenty lead-exposed men were selected on the basis of a maximum level of lead in the blood of 70-140 μg/100 ml within the past year. There was no clinical evidence of neuropathy attributable to lead and haemoglobin levels were normal. In individuals, maximum motor and sensory conduction and the amplitude of the evoked potentials were normal or borderline in the median, peroneal and sural nerves, except in the distal portion of the deep peroneal nerve. In this nerve, motor conduction was slowed because of compression by metal-lined safety shoes; changes in this segment are not included in the findings. When the average conduction velocity in lead-exposed men was compared with the average in nerves of controls matched for age, distal motor latency was slightly prolonged in the median nerve. The average latency for proximal muscle supplied by the peroneal nerve was prolonged, and the maximum motor conduction velocity was slowed in the median nerve from elbow to wrist (0·01 > p <0·001). In addition, the average maximum sensory conduction was slightly slowed along the distal and intermediate portion of the superficial peroneal and sural nerves (p <0·001). The average minimum sensory conduction velocities were normal, as were the average amplitudes of the evoked muscle action potentials and the average ratio of amplitude of the muscle action potential evoked by stimuli at a proximal and a distal nerve site. The average amplitude of the sensory potentials recorded in the median and the superficial peroneal nerves tended to be increased. Electromyography of the abductor pollicis brevis and anterior tibial muscles showed that the only abnormality was an increased incidence of polyphasic potentials in the anterior tibial muscle of seven men. Neither the slowing in conduction nor the histological findings in the sural nerves of eight men were related to the level of lead in the blood. The slight slowing in conduction suggests a minor defect in the excitable membrane of the nerve fibre: it was not attributable to histological abnormalities in the sural nerve, in which the number of myelinated and unmyelinated nerve fibres was normal and demyelination was absent. In teased fibres, those with paranodal remyelination were slightly increased, and few fibres had segments with diminished diameter. The mechanism of the defect causing the slight slowing in conduction in lead-exposed men seems to differ from the lesion in patients with clinical evidence of lead neuropathy, which is axonal in type. It is, therefore, doubtful whether the slight slowing in the nerves of the group of lead-exposed men should be classified as a subclinical neuropathy.
Single unit activity in spindle afferent nerve fibres from the finger flexors, the anterior tibial muscle, and the calf muscles was recorded intraneurally with tungsten microelectrodes in patients with Parkinsonism with resting tremor and in spastic patients with clonus. During tremor of Parkinsonism, involving the receptor bearing muscles, the Ia afferent fibre discharge patterns were similar to those seen previously in healthy subjects during voluntary fast alternating finger or foot movements: besides the stretch discharges occurring during the relaxation phases, discharges also occurred during the contraction phases. Such contraction discharges, presumed to originate from intrafusal muscle fibre contractions, were not seen in the spastic patients during clonus. During the clonic oscillations each afferent stretch discharge was regularly followed by a stretch reflex contraction which on its falling phase elicited a new volley of impulses in the Ia afferent fibres. The findings are considered to support the notion that, like the contractions in normal voluntary alternating movements, the contractions in tremor of Parkinsonism are organized according to the principle of alpha-gamma coactivation, whereas the contractions in clonus are stretch reflexes causing pure alpha contractions.
The flexion reflex can be elicited via stimulation of skin, muscle, and high-threshold afferents inducing a generalized flexion of the limb. In spinalized animal models this reflex is quite prominent and is strongly modulated by actions of hip proprioceptors. However, analogous actions on the flexion reflex in spinal cord injured (SCI) humans have not yet been examined. In this study, we investigated the effects of imposed static hip angle changes on the flexion reflex in ten motor incomplete SCI subjects when input from plantar cutaneous mechanoreceptors was also present. Flexion reflexes were elicited by low-intensity stimulation of the sural nerve at the lateral malleolus, and were recorded from the ipsilateral tibialis anterior (TA) muscle. Plantar skin stimulation was delivered through two surface electrodes placed on the metatarsals, and was initiated at different delays ranging from 3 to 90 ms. We found that non-noxious sural nerve stimulation induced two types of flexion reflexes in the TA muscle, an early, and a late response. The first was observed only in three subjects and even in these subjects, it appeared irregularly. In contrast, the second (late) flexion reflex was present uniformly in all ten subjects and was significantly modulated during hip angle changes. Flexion reflexes recorded with hip positioned at different angles were compared to the associated control reflexes recorded with hip flexed at 10°. Hip flexion (30°, 40°) depressed the late flexion reflex, while no significant effects were observed with the hip set in neutral angle (0°). Strong facilitatory effects on the late flexion reflex were observed with the hip extended to 10°. Moreover, the effects of plantar skin stimulation on the flexion reflex were also found to depend on the hip angle. The results suggest that hip proprioceptors and plantar cutaneous mechanoreceptors strongly modulate flexion reflex pathways in chronic human SCI, verifying that this type of sensory afferent feedback interact with spinal interneuronal circuits that have been considered as forerunners of stepping and locomotion. The sensory consequences of this afferent input should be considered in rehabilitation programs aimed to restore movement and sensorimotor function in these patients.
Cutaneous afferents; Flexion reflex; Hip proprioceptors; Rehabilitation; Sensorimotor integration
In neutral spinal postures with low loading moments the lumbar spine is not inherently stable. Small compromises in paraspinal muscle activity may affect lumbar spinal biomechanics. Proprioceptive feedback from muscle spindles is considered important for control of muscle activity. Because skeletal muscle and muscle spindles are thixotropic, their length history changes their physical properties. The present study explores a mechanism that can affect the responsiveness of paraspinal muscle spindles in the lumbar spine.
This study had two aims: to extend our previous findings demonstrating the history dependent effects of vertebral position on the responsiveness of lumbar paraspinal muscle spindles; and to determine the time course for these effects. Based upon previous studies, if a crossbridge mechanism underlies these thixotropic effects, then the relationship between the magnitude of spindle discharge and the duration of the vertebral position will be one of exponential decay or growth.
A neurophysiological study using the lumbar spine of a feline model.
The discharge from individual muscle spindles afferents innervating lumbar paraspinal muscles in response to the duration and direction of vertebral position were obtained from teased filaments in the L6 dorsal roots of 30 Nembutal-anesthetized cats. The L6 vertebra was controlled using a displacement-controlled feedback motor and was held in each of 3 different conditioning positions for durations of 0, 0.5, 1, 1.5, and 2 seconds. Two of the conditioning positions stretched or shortened the lumbar muscles relative to an intermediate conditioning position. Conditioning positions for all cats ranged from 0.9 – 2.0 mm dorsal and ventralward relative to the intermediate position. These magnitudes were determined based upon the displacement that loaded the L6 vertebra to 50–60% of the cat’s body weight. Conditioning was thought to simulate a motion segment’s position that might be passively maintained due to fixation, external load, a prolonged posture, or structural change. Following conditioning positions that stretched (hold-long) and shortened (hold-short) the spindle, the vertebra was repositioned identically and muscle spindle discharge at rest and to movement was compared with conditioning at the intermediate position.
Lumbar vertebral positions maintained for less than 2 seconds were capable of evoking different discharge rates from lumbar paraspinal muscle spindles despite the vertebra having been returned to identical locations. Both resting spindle discharge and their responsiveness to movement were altered. Conditioning vertebral positions that stretched the spindles decreased spindle activity and positions that unloaded the spindles increased spindle activity upon returning the vertebra to identical original (intermediate) positions. The magnitude of these effects increased as conditioning duration increased to 2 seconds. These effects developed with a time course following a first order exponential reaching a maximal value after approximately 4 seconds of history. The time constant for a hold-short history was 2.6 seconds and for a hold-long history was approximately half of that at 1.1 seconds.
Thixotropic contributions to the responsiveness of muscles spindles in the low back are caused by the rapid, spontaneous formation of stable crossbridges. These sensory alterations due to vertebral history would represent a proprioceptive input not necessarily representative of the current state of intersegmental positioning. As such, they would constitute a source of inaccurate sensory feedback. Examples are presented suggesting ways in which this novel finding may affect spinal physiology.
Ih, which influences neuronal excitability, has recently been measured in vivo in sensory neuron subtypes in dorsal root ganglia (DRGs). However, expression levels of HCN (hyperpolarization-activated cyclic nucleotide-gated) channel proteins that underlie Ih were unknown. We therefore examined immunostaining of the most abundant isoforms in DRGs, HCN1 and HCN2 in these neuron subtypes. This immunostaining was cytoplasmic and membrane-associated (ring). Ring-staining for both isoforms was in neurofilament-rich A-fiber neurons, but not in small neurofilament-poor C-fiber neurons, although some C-neurons showed cytoplasmic HCN2 staining. We recorded intracellularly from DRG neurons in vivo, determined their sensory properties (nociceptive or low-threshold-mechanoreceptive, LTM) and conduction velocities (CVs). We then injected fluorescent dye enabling subsequent immunostaining. For each dye-injected neuron, ring- and cytoplasmic-immunointensities were determined relative to maximum ring-immunointensity. Both HCN1- and HCN2-ring-immunointensities were positively correlated with CV in both nociceptors and LTMs; they were high in Aβ-nociceptors and Aα/β-LTMs. High HCN1 and HCN2 levels in Aα/β-neurons may, via Ih, influence normal non-painful (e.g. touch and proprioceptive) sensations as well as nociception and pain. HCN2-, not HCN1-, ring-intensities were higher in muscle spindle afferents (MSAs) than in all other neurons. The previously reported very high Ih in MSAs may relate to their very high HCN2. In normal C-nociceptors, low HCN1 and HCN2 were consistent with their low/undetectable Ih. In some C-LTMs HCN2-intensities were higher than in C-nociceptors. Together, HCN1 and HCN2 expressions reflect previously reported Ih magnitudes and properties in neuronal subgroups, suggesting these isoforms underlie Ih in DRG neurons. Expression of both isoforms was NT3-dependent in cultured DRG neurons. HCN2-immunostaining in small neurons increased 1 day after cutaneous inflammation (CFA-induced) and recovered by 4 days. This could contribute to acute inflammatory pain. HCN2-immunostaining in large neurons decreased 4 days after CFA, when NT3 was decreased in the DRG. Thus HCN2-expression control differs between large and small neurons.