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.
Single unit activity in primary spindle afferent nerve fibres from finger and foot flexors was recorded with tungsten microelectrodes inserted into the median and peroneal nerves of healthy subjects. During voluntary fast alternating finger and foot movements, simulating the tremor of Parkinsonism, two types of discharges were seen in the Ia afferent fibres: (1) stretch responses occurring during the flexor relaxation phases, and (2) discharges occurring during the flexor contraction phases. Contrary to the stretch responses the spindle contraction discharges could be eliminated by a partial lidocaine block of the muscle nerve proximal to the recording site, indicating that they resulted from fusimotor activation of intrafusal fibres. On the basis of the temporal relations between the beginning and end of individual EMG-bursts, the start of the spindle contraction discharges and the latency of the stretch reflex in the muscles concerned, the following conclusions were drawn: the recurrent extrafusal contractions in movements of this type are initiated by the fast direct alpha route, but individual contraction phases generally last long enough to be influenced subsequently by the coactivated fusimotor loop through the spindles. It is postulated that this gamma loop influence during alternating movements helps to keep flexor and extensor muscles working in a regular reciprocal fashion with contractions adjusted in strength to the external loads.
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 contribution of the fusimotor system to reflex reinforcement such as the Jendrassik manoeuvre was investigated by recording single unit activity with tungsten electrodes from muscle spindle afferent nerves in unanaesthetized normal human subjects. Muscle spindle afferent activity was recorded before, during, and after the reinforcement test. When the leg muscles remained relaxed during the Jendrassik manoeuvre, spindle activity recorded in the tibial nerve was accelerated. Also in the median nerve, activity from muscle spindle afferent fibres was increased during a remote contraction of the ipsilateral quadriceps muscle. Comparing the time course of the phasic reflex reinforcement and the muscle spindle facilitation during the remote contraction, a marked after-effect was recorded in both responses. Present results show an increased spontaneous muscle spindle activity in relaxed muscles during a remote muscle contraction, and provide evidence for the contribution of the fusimotor system to the enhancement of phasic reflexes by reinforcement manoeuvres.
Twenty-five cases of peroneal muscular atrophy with pyramidal features from 15 families are described. This disorder has been referred to as hereditary motor and sensory neuropathy (HMSN) type V by Dyck. Onset was usually in the first two decades of life with difficulty in walking. The clinical syndrome superficially resembled that of HMSN types I and II with distal wasting and weakness involving the legs more than the arms. The tendon reflexes in the upper limbs and at the knee tended to be normal or increased but the ankle jerks were often absent. The plantar responses were extensor in 22 patients, absent in two and flexor in one. Increased tone and weakness in the proximal lower limb muscles were found in about 30% of cases. Mean motor nerve conduction velocity was lower than in normal controls and sensory nerve action potentials were reduced in amplitude or absent in two thirds of the patients studied. Inheritance was autosomal dominant in the majority of families. The disorder was slowly progressive but did not lead to severe disability.
Induced pluripotent stem (iPS) cells have considerable promise as a novel tool for modelling human disease and for drug discovery. While the generation of disease-specific iPS cells has become routine, realizing the potential of iPS cells in disease modelling poses challenges at multiple fronts. Such challenges include selecting a suitable disease target, directing the fate of iPS cells into symptom-relevant cell populations, identifying disease-related phenotypes and showing reversibility of such phenotypes using genetic or pharmacological approaches. Finally, the system needs to be scalable for use in modern drug discovery. Here, we will discuss these points in the context of modelling familial dysautonomia (FD, Riley–Day syndrome, hereditary sensory and autonomic neuropathy III (HSAN-III)), a rare genetic disorder in the peripheral nervous system. We have demonstrated three disease-specific phenotypes in FD-iPS-derived cells that can be partially rescued by treating cells with the plant hormone kinetin. Here, we will discuss how to use FD-iPS cells further in high throughput drug discovery assays, in modelling disease severity and in performing mechanistic studies aimed at understanding disease pathogenesis. FD is a rare disease but represents an important testing ground for exploring the potential of iPS cell technology in modelling and treating human disease.
human induced pluripotent stem cells; disease modelling; peripheral nervous system; human genetic disease; stem cells; drug discovery
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.
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.
Microneurography was performed in median nerve sensory fascicles with concentric needle electrodes and with conventional tungsten microneedles. The latter electrodes preferentially recorded activity from the myelinated fibres in the whole fascicle. By contrast, due to its special design, a concentric needle can record activity selectively from even a small part of a fascicle. High amplitude signals in C fibres can be discriminated close to Schwann cells that envelope unmyelinated axons. Apart from being biased for activity in thin fibres, the concentric needles can also record signals from nearby myelinated fibres. The palmar receptive fields of such fibre groups were not congruent with the areas traditionally attributed to multiunit skin afferents in humans, namely the innervation zone(s) of one or two adjacent digital nerve(s). Instead, the multiunit fields often comprised small parts of a digital nerve innervation area, frequently only the pulp of a finger. Single units were always localised within previously screened multiunit areas. Contrary to some previously accepted tenets it is probable that single unit activity in myelinated fibres in these studies is recorded extra-axonally near to a node of Ranvier. The findings also suggest the presence of a somatotopy in human limb nerve fascicles, comparable to that previously established in the spinal cord and the somatosensory cortex.
The syndrome of cerebellar ataxia with bilateral vestibulopathy was delineated in 2004. Sensory neuropathy was mentioned in 3 of the 4 patients described. We aimed to characterize and estimate the frequency of neuropathy in this condition, and determine its typical MRI features.
Retrospective review of 18 subjects (including 4 from the original description) who met the criteria for bilateral vestibulopathy with cerebellar ataxia.
The reported age at onset range was 39–71 years, and symptom duration was 3–38 years. The syndrome was identified in one sibling pair, suggesting that this may be a late-onset recessive disorder, although the other 16 cases were apparently sporadic. All 18 had sensory neuropathy with absent sensory nerve action potentials, although this was not apparent clinically in 2, and the presence of neuropathy was not a selection criterion. In 5, the loss of pinprick sensation was virtually global, mimicking a neuronopathy. However, findings in the other 11 with clinically manifest neuropathy suggested a length-dependent neuropathy. MRI scans showed cerebellar atrophy in 16, involving anterior and dorsal vermis, and hemispheric crus I, while 2 were normal. The inferior vermis and brainstem were spared.
Sensory neuropathy is an integral component of this syndrome. It may result in severe sensory loss, which contributes significantly to the disability. The MRI changes are nonspecific, but, coupled with loss of sensory nerve action potentials, may aid diagnosis. We propose a new name for the condition: cerebellar ataxia with neuropathy and bilateral vestibular areflexia syndrome (CANVAS). Neurology® 2011;76:1903–1910
Despite the clinical significance of muscle pain, and the extensive investigation of the properties of muscle afferent fibers, there has been little study of the ion channels on sensory neurons that innervate muscle. In this study, we have fluorescently tagged sensory neurons that innervate the masseter muscle, which is unique because cell bodies for its muscle spindles are in a brainstem nucleus (mesencephalic nucleus of the 5th cranial nerve, MeV) while all its other sensory afferents are in the trigeminal ganglion (TG). We examine the hypothesis that certain molecules proposed to be used selectively by nociceptors fail to express on muscle spindles afferents but appear on other afferents from the same muscle.
MeV muscle afferents perfectly fit expectations of cells with a non-nociceptive sensory modality: Opiates failed to inhibit calcium channel currents (ICa) in 90% of MeV neurons, although ICa were inhibited by GABAB receptor activation. All MeV afferents had brief (1 msec) action potentials driven solely by tetrodotoxin (TTX)-sensitive Na channels and no MeV afferent expressed either of three ion channels (TRPV1, P2X3, and ASIC3) thought to be transducers for nociceptive stimuli, although they did express other ATP and acid-sensing channels. Trigeminal masseter afferents were much more diverse. Virtually all of them expressed at least one, and often several, of the three putative nociceptive transducer channels, but the mix varied from cell to cell. Calcium currents in 80% of the neurons were measurably inhibited by μ-opioids, but the extent of inhibition varied greatly. Almost all TG masseter afferents expressed some TTX-insensitive sodium currents, but the amount compared to TTX sensitive sodium current varied, as did the duration of action potentials.
Most masseter muscle afferents that are not muscle spindle afferents express molecules that are considered characteristic of nociceptors, but these putative muscle nociceptors are molecularly diverse. This heterogeneity may reflect the mixture of metabosensitive afferents which can also signal noxious stimuli and purely nociceptive afferents characteristic of muscle.
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
The following is a case report which reviews the essential aspects of Lambert–Eaton myasthenic syndrome (LEMS) in a patient with long standing back pain and gait dysfunction. The patient was referred to our electrodiagnostics laboratory for a 9-month history of low back pain and difficulty walking following a charity breast cancer walk. A workup including magnetic resonance imaging of the brain, entire spine, and EMG/NCS at another institution were reportedly normal. A detailed history revealed symptoms of proximal weakness and autonomic dysfunction. Physical findings were consistent with proximal weakness, a bilateral gluteus medius gait, and diffusely absent reflexes obtainable in the biceps after 3 s of contraction. Electrical testing revealed an initial low compound muscle action potential amplitude in the deep peroneal nerve recording from the extensor digitorum brevis. Repetitive stimulation at 2 Hz revealed a decremental response of 42% from the 1st response to the 4th response. Following 3 s of exercise, the amplitude increased by 300%. After 30 s of exercise followed by 1 min of rest, there was a return of the decremental response. The history, physical examination, and electrical findings were illustrative of a presynaptic neuromuscular junction disorder, specifically LEMS.
Lambert–Eaton myasthenic syndrome; Neuromuscular junction; Proximal weakness; Low back pain; Repetitive stimulation
tropical ataxic neuropathy (TAN) is currently used to describe several
neurological syndromes attributed to toxiconutritional causes. However,
TAN was initially proposed to describe a specific neurological syndrome
seen predominantly among the Ijebu speaking Yorubas in south western
Nigeria. In this study, the prevalence of TAN was determined in Ososa,
a semiurban community in south western Nigeria described as endemic for
TAN in 1969, and its neurological features were compared with
Strachan's syndrome, prisoners of war neuropathy, the epidemic
neuropathy in Cuba, and konzo.
METHODS—A census of
Ososa was followed by door to door screening of all subjects aged 10 years and above with a newly designed screening instrument. Subjects
who screened positive had a neurological examination, and the diagnosis
of TAN was made if any two or more of bilateral optic atrophy,
bilateral neurosensory deafness, sensory gait ataxia, or distal
symmetric sensory polyneuropathy were present.
RESULTS—A total of
4583 inhabitants were registered in the census. Of these, 3428 subjects
aged 10 years and above were screened. The diagnosis of TAN was made in
206 of 323 subjects who screened positive for TAN. The prevalence of
TAN was 6.0%, 3.9% in males and 7.7% in females. The highest age
specific prevalence was 24% in the 60-69 years age group in women.
occurrence of TAN in Ososa continues at a higher prevalence than was
reported 30 years ago. Its neurological features and natural history do
not resemble those described for Strachan syndrome, epidemic neuropathy
in Cuba, or konzo. The increasing consumption of cassava foods linked
to its causation makes TAN of public health importance in Nigeria, the
most populous African country.
Sensory conduction was studied in six patients with chronic sensory ataxic neuropathy of an idiopathic type and associated with Sjögren's syndrome. Motor nerve conduction velocities were normal in most cases, but sensory nerve potentials could not be evoked in a routine peripheral nerve conduction study. Cortical and cervical somatosensory evoked potentials (SEPs) and evoked potentials from Erb's point were barely recorded by median nerve stimulation at the wrist. When the median nerve was stimulated at more proximal points, clear potentials were recorded from Erb's point, but cortical SEPs were still hardly elicited. Thus the sensory nerves are centrally and peripherally involved in this condition, and the involvement is more prominent in the distal portion in the peripheral nerve. These findings suggest that central-peripheral distal axonopathy is a process involved in this illness and that the dorsal root ganglia may be primarily involved, in accord with previous pathological studies.
Neurotrophin-3 (NT-3), a member of the neurotrophin family, has
been shown to be necessary for the development of muscle spindle and
Merkel cell afferent nerve fibres in animal models.The presence of NT-3
in the suprabasal epidermis, where many unmyelinated sensory fibres
terminate, has been shown for the first time. As these fibres are
affected in early diabetic neuropathy and a clinical trial of
recombinant human NT-3 in diabetic neuropathy is in progress, the
concentrations of endogenous NT-3 in skin of 24 patients at different
stages of diabetic polyneuropathy have been investigated. NT-3
concentrations, measured with a specific immunoassay, were significantly higher in affected skin biopsies from patients with diabetic neuropathy than matched control skin (diabetic skin 6.32(1.18) pg/mg v control skin 1.28 (0.05)
(mean (SEM)); p<0.004, Mann-Whitney U
test), particularly in the later stages. The optical density of
NT-3-immunostaining was also significantly greater in the epidermis in
diabetic patients (diabetic epidermis 0.30(0.06)
v controls 0.24 (0.01); p<0.02). No
correlation was found between individual quantitative sensory tests and
the increase of NT-3 concentration. The increase of NT-3 seems to
reflect the degree of skin denervation in diabetic neuropathy, and may
represent a compensatory mechanism. The concentrations of NT-3 in other peripheral targets deserve study in diabetic neuropathy.
After peripheral nerve injuries to a motor nerve the axons of motoneurons and proprioceptors are disconnected from the periphery and monosynaptic connections from group I afferents and motoneurons become diminished in the spinal cord. Following successful reinnervation in the periphery, motor strength, proprioceptive sensory encoding, and Ia afferent synaptic transmission on motoneurons partially recover. Muscle stretch reflexes, however, never recover and motor behaviors remain uncoordinated. In this review, we summarize recent findings that suggest that lingering motor dysfunction might be in part related to decreased connectivity of Ia afferents centrally. First, sensory afferent synapses retract from lamina IX causing a permanent relocation of the inputs to more distal locations and significant disconnection from motoneurons. Second, peripheral reconnection between proprioceptive afferents and muscle spindles is imperfect. As a result, a proportion of sensory afferents that retain central connections with motoneurons might not reconnect appropriately in the periphery. A hypothetical model is proposed in which the combined effect of peripheral and central reconnection deficits might explain the failure of muscle stretch to initiate or modulate firing of many homonymous motoneurons.
stretch reflex; spinal cord; plasticity; motor control; adult
Familial burning feet syndrome inherited as an autosomal
dominant trait has been described in only one family. Due to an
associated sensory neuropathy the autosomal dominant burning feet
syndrome was suggested to represent a variant form of hereditary
sensory and autonomic neuropathy type I (HSAN I). Clinical,
histopathological, and molecular genetic studies were performed in a
large German kindred with autosomal dominant burning feet syndrome. The
autosomal dominant burning feet syndrome was associated with a
neuropathy predominantly affecting small unmyelinated nerve fibres.
Linkage to the HSAN I locus on chromosome 9q22 and to the
Charcot-Marie-Tooth disease type 2B (CMT 2B) locus on chromosome
3q13-q22 was excluded. The autosomal dominant burning feet syndrome is
neither allelic to HSAN I nor to CMT 2B and thus represents a distinct
A syndrome is described, consisting of severe neurogenic distal wasting, generalised muscle weakness, absent ankle reflexes, pyramidal signs, mental retardation, optic atrophy and retinal colloid bodies. A sural nerve biopsy from one case showed loss of nerve fibres suggesting the diagnosis of hereditary motor and sensory neuropathy. Progression of the disorder was very slow, all patients still being able to walk more than 20 years after the onset. The persons affected with this syndrome were two brothers and their female cousin from a large Gujerati pedigree where consanguinity was high. Autosomal recessive inheritance is therefore suggested.
Neurological affection in Sjogren's syndrome (SS) can occur in the central and peripheral nervous system. Literature describing the neurological involvement in SS among Indian patients is lacking.
Materials and Methods:
Six patients of SS fulfilling the histological or serological criteria of the American European Consensus Group for SS were studied prospectively. The patients underwent clinical examination and laboratory investigations. Their clinical and investigation features are described.
The age of the patients ranged from 26 to 48 years, with a male to female ratio of 2:4. In our series, peripheral sensori-motor neuropathy and sensory ataxic neuropathy was seen in 3/6, mononeuritis multiplex in 2/6, cranial neuropathy in 2/6, autonomic neuropathy in 1/6, myelopathy in 4/6, optic neuropathy in 2/6, with presence of classical sicca features in 5/6 patients. Positive lip biopsy was seen in three, altitudinal field defect in one and positive Schirmer's test in five patients. Nerve conduction study abnormalities were seen in three and evidence of vasculitis was seen in nerve biopsy of one patient and chronic nonuniform axonopathy was seen in another. Antibody to Ro (SSA) or La (SSB) was positive in five patients.
SS involves different parts of the nervous system with varied presentations. Clinical suspicion and adequate laboratory testing helps to diagnose and manage this disorder that is relatively rare in Indian patients.
Myelitis; polyneuropathies; Sjogren's syndrome; trigeminal neuropathy
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.
Background and Purpose
The potential association between the severity of autonomic dysfunction and peripheral neuropathy has not been extensively investigated, with the few studies yielding inconsistent results. We evaluated the relationship between autonomic dysfunction and peripheral neuropathy in chronic hemodialysis patients in a cross-sectional study.
Cardiovascular autonomic function was assessed in 42 consecutive patients with chronic renal failure treated by hemodialysis, using a standardized battery of 5 cardiovascular reflex tests. Symptoms of autonomic dysfunction and of peripheral neuropathy were evaluated using the Autonomic Neuropathy Symptom Score (ANSS) and the Neuropathy Symptoms Score. Neurological deficits were assessed using the Neuropathy Disability Score. Conduction velocities along the sensory and motor fibers of the sural and peroneal nerves were measured. Thermal thresholds were documented using a standardized psychophysical technique.
Parasympathetic and sympathetic dysfunction was prevalent in 50% and 28% of cases, respectively. Peripheral neuropathy was identified in 25 cases (60%). The prevalence of peripheral neuropathy did not differ between patients with impaired (55%) and normal (75%) autonomic function (p=0.297; Fisher's exact test). The electrophysiological parameters for peripheral nerve function, neuropathic symptoms, abnormal thermal thresholds, age, gender, and duration of dialysis did not differ significantly between patients with and without autonomic dysfunction. Patients with autonomic dysfunction were more likely to have an abnormal ANSS (p=0.048). The severity of autonomic dysfunction on electrophysiological testing was positively correlated with ANSS (r=0.213, p=0.036).
The present data indicate that although cardiovascular autonomic dysfunction is prevalent among patients with chronic renal failure, it is not associated with the incidence of peripheral neuropathy.
autonomic dysfunction; hemodialysis; neuropathy; cardiovascular reflexes
Clinical findings: Onset was in early childhood with gait difficulty related to progressive lower limb weakness. Upper limb weakness developed later. Bulbar involvement was present in one third of the patients, and deafness appeared during the second or third decades.
Electrophysiological findings: Electromyographic evidence of denervation was progressive, more severe distally, and greater in the legs, being total in distal lower limb muscles in most patients. Sensory action potentials were absent and motor nerve conduction was severely slowed. This included proximal upper limb (musculocutaneous and axillary), hypoglossal, and facial nerves. The severity of slowing increased during childhood. M waves, often multiple, were recorded in all affected individuals. The blink reflex showed an unusual three component response. The latencies of all three components were prolonged.
Conclusions: HMSN-L is shown to be a demyelinating neuropathy involving severe and early axonal loss. The progressive slowing of nerve conduction during childhood differs from the static reduction seen in type I HMSN.
Hereditary neuropathy with liability to pressure palsy (HNPP) is characterized by recurrent focal neuropathies, which usually become symptomatic in the second or third decade of life. However, clinical phenotypic heterogeneity among patients with HNPP has recently been reported. Certain patients show polyneuropathy-type diffuse nerve injuries, whereas others remain asymptomatic at older ages. We present two cases of elderly-onset bilateral peroneal nerve palsies with diffuse muscle weakness in the lower limbs and glove-and-stocking type sensory disturbance. Both patients were diagnosed with HNPP by genetic analyses that detected deletions of chromosome 17p11.2 in peripheral myelin protein 22 genes. Their clinical courses suggested that the Japanese sitting style termed ‘seiza’, a way of sitting on the floor with the lower legs crossed under the thighs, was a precipitating factor for the bilateral peroneal nerve palsies.
Hereditary neuropathy with liability to pressure palsy; Elderly-onset; Bilateral peroneal nerve palsies; Peripheral myelin protein 22; ‘Seiza’
In a review of twelve cases of Friedreich's ataxia, the important criteria for early diagnosis were identified. Clinical signs included absent tendon reflexes, ataxic gait, and a positive Romberg test. Nerve conduction velocities showed absent or severely slowed sensory conduction, with normal motor conduction. In addition, echocardiographic changes of symmetrical hypertrophic cardiomyopathy were found.