Background & objectives:
There is paucity of studies on the quality of anticoagulation in neurological patients from India. This study evaluates the quality of oral anticoagulation therapy in neurology patients.
Consecutive patients attending a tertiary care neurology service in north India who were prescribed oral anticoagulant (OAC), were included. Their international normalized ratio (INR) values were prospectively monitored and the earlier INR values of the patients who were already on OAC were retrospectively analyzed. The patients with multi-organ dysfunction, pregnancy and those below 18 yr of age were excluded. The therapeutic INR range was defined as per standard recommendations. The level of anticoagulation, factors interfering with OAC and complications were noted.
The results were based on 77 patients with median age 40 yr. Fifty one patients received OAC for secondary stroke prevention, 23 for cerebral venous sinus thrombosis (CVST) and three for deep vein thrombosis (DVT). A total 167.9 person-years of follow up was done with a median of 1.2 (0.3-9.3) years. Of the 1287 INR reports, 505 (39.3%) reports were in the therapeutic range, 496 (38.5%) were below and 282 (21.91%) were above the therapeutic level. Stable INR was obtained in 33 (42.86%) patients only. INR level was improved by dose adjustment in 20 (26%), drug modification in two (2.6%), and dietary adjustment in six (7.8%) patients. Three patients were sensitive and five were resistant to OAC. Complications were noted in 28 instances; thromboembolic in 16 and haemorrhagic stroke in 12. The overall complication rate was 16.7 per 100 person-years.
Interpretation & conclusions:
It may be concluded that stable therapeutic INR is difficult to maintain in neurological patients. Optimal modification of diet, drug and dose of oral anticoagulant may help in stabilization of INR.
Complications; INR; nicoumalone; oral anticoagulation; stroke; warfarin
There is paucity of reports on thyrotoxic periodic paralysis (TPP) from India. We report the patients with TPP and compare them with idiopathic hypokalemic periodic paralysis (IHPP).
Materials and Methods:
Patients with hypokalemic periodic paralysis (HPP) treated during the past 11 years were evaluated retrospectively. Their demographic parameters, family history, clinical features, precipitating factors, severity of weakness, laboratory parameters and rapidity of recovery were recorded. The demographic, clinical and laboratory parameters of TPP and IHPP were compared.
During the study period, we managed 52 patients with HPP; nine (17.3%) of whom had TPP and 27 (52%) had IHPP. The demographic, precipitating factors, number of attacks and severity of limb weakness were similar between the TPP and IHPP groups, except in the IHPP group, bulbar weakness was present in four and respiratory paralysis in six, needing artificial ventilation in two patients. Serum potassium was significantly lower in TPP (2.21 ± 0.49) compared with IHPP (2.67 ± 0.59, P = 0.04). Four patients with TPP had subclinical thyrotoxicosis and two had subclinical hyperthyroidism. Rebound hyperkalemia occurred in both TPP and IHPP (three versus eight patients). The recovery was faster in IHPP (26.7 ± 15.4 h) compared with TPP (34.0 ± 14.0 h), but was statistically insignificant.
TPP constitutes 17.3% of HPP, and absence of clinical features of thyrotoxicosis and subclinical hyperthyroidism in TPP is not uncommon. Clinical features, demographic profile and rebound hyperkalemia are similar in both TPP and IHPP. The serum potassium level is significantly low in the TPP compared with the IHPP group.
Hypokalemia; hypokalemic periodic paralysis; periodic paralysis; thyrotoxic periodic paralysis; treatment
In epilepsy, in spite of the best possible medications and treatment protocols, approximately one-third of the patients do not respond adequately to anti-epileptic drugs. Such interindividual variations in drug response are believed to result from genetic variations in candidate genes belonging to multiple pathways.
MATERIALS AND METHODS:
In the present pharmacogenetic analysis, a total of 402 epilepsy patients were enrolled. Of them, 128 were diagnosed as multiple drug-resistant epilepsy and 274 patients were diagnosed as having drug-responsive epilepsy. We selected a total of 10 candidate gene polymorphisms belonging to three major classes, namely drug transporters, drug metabolizers and drug targets. These genetic polymorphism included CYP2C9 c.430C>T (*2 variant), CYP2C9 c.1075 A>C (*3 variant), ABCB1 c.3435C>T, ABCB1c.1236C>T, ABCB1c.2677G>T/A, SCN1A c.3184 A> G, SCN2A c.56G>A (p.R19K), GABRA1c.IVS11 + 15 A>G and GABRG2 c.588C>T. Genotyping was performed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methods, and each genotype was confirmed via direct DNA sequencing. The relationship between various genetic polymorphisms and responsiveness was examined using binary logistic regression by SPSS statistical analysis software.
CYP2C9 c.1075 A>C polymorphism showed a marginal significant difference between drug resistance and drug-responsive patients for the AC genotype (Odds ratio [OR] = 0.57, 95% confidence interval [CI] = 0.32–1.00; P = 0.05). In drug transporter, ABCB1c.2677G>T/A polymorphism, allele A was associated with drug-resistant phenotype in epilepsy patients (P = 0.03, OR = 0.31, 95% CI = 0.10-0.93). Similarly, the variant allele frequency of SCN2A c.56 G>A single nucleotide polymorphism was significantly higher in drug-resistant patients (P = 0.03; OR = 1.62, 95% CI = 1.03, 2.56). We also observed a significant difference at the genotype as well as allele frequencies of GABRA1c.IVS11 + 15 A > G polymorphism in drug-resistant patients for homozygous GG genotype (P = 0.03, OR = 1.84, 95% CI = 1.05–3.23) and G allele (P = 0.02, OR = 1.43, 95% CI = 1.05–1.95).
Our results showed that pharmacogenetic variants have important roles in epilepsy at different levels. It may be noted that multi-factorial diseases like epilepsy are also regulated by various other factors that may also be considered in the future.
Drug resistance; epilepsy; pharmacogenomics
We report three children with pseudohypoparathyroidism aged 13-16 years who presented with seizures and tetany. CT scan revealed striatopallidal calcification in two. MRI revealed wide-spread involvement showing T1 hyperintensity in striatopallidodentate distribution in all three and midbrain in one patient. T2 and FLAIR images were normal. T1 hyperintensity could represent early stage of calcification in whom MRI is more sensitive.
CT scan; MRI; parathormone; pseudohypoparathyroidism
Background and aims
This study was undertaken to compare the clinical and electrodiagnostic (Edx) features in autoimmune and nutritional vitamin B12 deficiency neurological syndromes.
Consecutive patients with vitamin B12 deficiency neurological syndromes were evaluated and blood counts, red blood cell indices, serum chemistry, thyroid function, HIV serology, antiparietal cell antibody (APCA), serum B12, bone marrow and spinal MRI assessed. EDx studies included nerve conduction, tibial somatosensory (SEP) and motor evoked potential (MEP) to the tibialis anterior, and visual evoked potential (VEP). The results were compared between APCA positive and negative groups.
57 patients aged 17–80 years (mean 45.3) were studied; 48 were vegetarians. The presenting clinical syndromes were myeloneuropathy in 25, myelopathy in 14, myeloneuroencephalopathy in 13, myeloencephalopathy in four and behavioural abnormality only in one patient. Spinal MRI in 47 patients revealed posterior spinal cord hyperintensity in 21 and cord atrophy in six. Nerve conduction was abnormal in 15%, MEP in 56.6%, SEP in 87.3% and VEP in 63.6% of patients. At 3 months, 31 patients had complete, 11 partial and three poor recovery. APCA was positive in 49% of patients. There was no difference in clinical, MRI or Edx findings or outcome between the APCA positive and negative groups.
APCA was positive in 49% of patients with B12 deficiency neurological syndrome but their clinical, MRI and Edx changes were not different from the APCA negative group. Neurological manifestations may be caused by B12 deficiency itself rather than the underlying cause.
Flexion myelopathy is one of the suggested mechanism for Hirayama disease (HD) but simultaneous radiological and neurophysiological evaluation is lacking. This study therefore evaluates the effect of neck flexion in HD using somatosensory evoked potentials (SEPs), F waves, and magnetic resonance imaging (MRI).
Eight HD patients and seven matched controls were subjected to median and ulnar F wave (minimal latency, FM ratio, persistence, and chronodispersion), and SEPs evaluating N9, N13, and N20 potentials in neutral and neck flexion. Spinal MRI was carried out in neutral and neck flexion and evaluated for cord atrophy, signal changes, cord compression, posterior epidural tissue, and loss of dural attachment.
The patients were aged 19 to 30 years. Minimal F latency, FM ratio, persistence, and chronodispersion in neutral and neck flexion did not show any change nor was there any change in N13 latency and amplitude on median and ulnar SEPs. The difference in these parameters in neutral and neck flexion were also not significant in HD compared with controls. The change in N13 was also not related to loss of dural attachment and posterior epidural tissue.
Neck flexion does not produce significant changes in N13 and F wave parameters and is not related to dynamic MRI changes. The other mechanisms for HD should therefore be explored.
F wave; Hirayama disease; magnetic resonance imaging; somatosensory evoked potential; neck flexion
Diabetic neuropathy (DN) refers to symptoms and signs of neuropathy in a patient with diabetes in whom other causes of neuropathy have been excluded. Distal symmetrical neuropathy is the commonest accounting for 75% DN. Asymmetrical neuropathies may involve cranial nerves, thoracic or limb nerves; are of acute onset resulting from ischaemic infarction of vasa nervosa. Asymmetric neuropathies in diabetic patients should be investigated for entrapment neuropathy. Diabetic amyotrophy, initially considered to result from metabolic changes, and later ischaemia, is now attributed to immunological changes. For diagnosis of DN, symptoms, signs, quantitative sensory testing, nerve conduction study, and autonomic testing are used; and two of these five are recommended for clinical diagnosis. Management of DN includes control of hyperglycaemia, other cardiovascular risk factors; α lipoic acid and L carnitine. For neuropathic pain, analgesics, non‐steroidal anti‐inflammatory drugs, antidepressants, and anticonvulsants are recommended. The treatment of autonomic neuropathy is symptomatic.
neuropathy; diabetes; treatment; classification; pathophysiology
Methods: The study included 43 patients with Pott's paraplegia, managed conservatively. The diagnosis of Pott's spine was based on clinical, magnetic resonance imaging, and computed tomography or ultrasound guided aspiration biopsy. All patients were examined clinically, and motor evoked potentials (MEPs) to lower limbs and tibial somatosensory evoked potentials (SEP) were recorded. Outcome at six months was defined as good or poor. For evaluating predictors of outcome, 15 clinical, investigative, and evoked potential variables were analysed, using multiple logistic regression analysis.
Results: The age range of the patients was 16–70 years, and 22 were female. Mild spasticity with hyperreflexia only was seen in 13 patients. In the remaining, weakness was severe in eight, and moderate and mild in 11 patients each. Twenty patients had loss of joint position sensation. MEP and SEP were abnormal in 19 and 18 patients, respectively. On multiple regression analysis, the best model predicting six month outcome included power, paraplegia score, SEP, and MEP.
Conclusion: Patients with Pott's paraplegia are likely to recover completely by six months if they have mild weakness, lower paraplegia score and normal SEPs and MEPs.
A 60-year-old male with chronic lymphatic leukemia (CLL) after 6 months of fludarabine therapy was admitted with status epilepticus and developed left hemiplegia. His magnetic resonance imaging revealed multiple T2 hyperintense lesions in the right frontal and left parieto-occipital lesion, simulating progressive multifocal leucoencephalopathy (PML). Cerebrospinal fluid Polymerase Chain Reaction (PCR) for JC virus was negative. We suggest the possible role of fludarabine in producing PML-like lesions in patients with Chronic Lymphocytic Leukemia (CLL).
Progressive multifocal leucoencephalopathy; chronic lymphocytic leukemia; fludarabine
Background: Rofecoxib is a potent cyclo-oxygenase-2 inhibitor with a long duration of action. Its role in migraine has not been systematically evaluated.
Aim: To study the efficacy of rofecoxib in migraine.
Method: In a randomised placebo controlled trial rofecoxib 25 mg, ibuprofen 400 mg, and placebo were compared regarding their efficacy in relieving acute migraine attack. Migraine patients with 2–6 attacks per month were recruited. Headache severity, functional disability, and severity of associated symptoms were graded on a 0–3 scale. The primary endpoint was pain relief at two hours. Relief of associated symptoms and sustained pain relief for 24 hours were also noted.
Result: One hundred and twenty four patients were randomised into rofecoxib (42), ibuprofen (40), and placebo (42) groups. One hundred and one patients were followed up: 33 on rofecoxib, 35 ibuprofen, and 33 placebo. Patients' ages ranged from 16–62 (mean 31.4) years, and 83 were females. Pain relief at two hours was noted in 45.5% on rofecoxib, 55.6% on ibuprofen, and 9.1% in the placebo group. The associated symptoms at two hours were reduced in 39.4% on rofecoxib, 50% on ibuprofen, and 9.1% in the placebo group. Sustained 24 hour pain relief was noted in 36.4% on rofecoxib, 41% on ibuprofen, and 6.1% in the placebo group. In the ibuprofen group, five patients had abdominal pain but there were no side effects in those on rofecoxib or in the control group. Both rofecoxib and ibuprofen were significantly effective in relieving pain, associated symptoms at two hours, and in sustained pain relief. There was no significant difference between rofecoxib and ibuprofen in aborting acute migraine attacks.
Conclusions: Both ibuprofen and rofecoxib were superior to placebo in aborting an acute migraine attack, and there was no significant difference in their efficacy in an acute migraine attack.
Aims: To evaluate micturition abnormalities in acute transverse myelitis and correlate these with evoked potentials, magnetic resonance imaging (MRI), and urodynamic findings.
Setting: Tertiary care teaching hospital.
Patients: 18 patients with acute transverse myelitis, aged 4–50 years; 15 had paraparesis and three quadriparesis.
Methods: Patients with acute transverse myelitis had a neurological evaluation and tibial somatosensory and motor evoked potential studies in the lower limbs. Spinal MRI was carried out using a 1.5 T scanner. Urodynamic studies were done using Dantec UD 5500 equipment. Neurological outcome was determined on the basis of Barthel index score at six months as poor, partial, or complete. In some patients, urodynamic studies were repeated at six and 12 months.
Results: Spinal MRI in 14 of the 18 patients revealed T2 hyperintense signal changes extending for at least three spinal segments in 13; one patient had normal MRI. In the acute stage, 17 patients had a history of urinary retention and one had urge incontinence. On follow up at six months two patients regained normal voiding, retention persisted in six, and storage symptoms developed in 10, of whom five also had emptying difficulties. Urodynamic studies showed an areflexic or hypocontractile bladder in 10, detrusor hyperreflexia with poor compliance in two, and detrusor sphincter dyssynergia in three. Early abnormal urodynamic findings commonly persisted at the six and 12 months examinations. Persistent abnormalities included detrusor hyperreflexia, dyssynergia, and areflexic bladder. The urodynamic abnormalities correlated with muscle tone and reflex changes but not with sensory or motor evoked potentials, muscle power, MRI signal changes, sensory level, or six months outcome.
Conclusions: Bladder dysfunction is common in acute transverse myelitis and may be the only sequel. Urodynamic study is helpful in evaluating the bladder dysfunction and also in its management.
Objectives: A number of movement disorders have been reported in Japanese encephalitis (JE). The prognostic significance of these movement disorders, however, has not been evaluated. The present study reports the prognostic significance of parkinsonian features and dystonia in JE.
Patients and methods: During 1992 and 1998, 50 JE patients were managed; 35 of them developed movement disorders (the study group). The diagnosis of JE was based on clinical, radiological, and serological criteria. Parkinsonian features were rated by the unified Parkinson's disease rating scale and dystonia by the dystonia rating scale. The patients with parkinsonian features only were classified into group I and those with additional dystonia or dyskinesia into group II. The outcome was defined at the end of three months into poor, partial, and complete recovery depending on how the patients coped with daily living activities.
Results: The patients' ages ranged from 2 to 64 years and 11 were females. The admission mean Glasgow coma scale score was 6.9 (range 4–13). The movement disorders were noted after 1–4 weeks of ictus. There were 16 patients in group I and 19 in group II. The parkinsonian features were more pronounced in group II than in group I. At three months of follow up, fewer patients had parkinsonian features in group I than group II. Hypophonia, however, persisted in 12 patients in group I and 16 in group II until the three month follow up. In group II, the mean dystonia score was 3.2 which regressed to 1.8 at three months. Tremor was present in five patients in groups I and eight in group II. Cranial computed tomography was abnormal in six and magnetic resonance imaging abnormal in 15 patients in group I and in nine and 12 patients respectively in group II. The thalamus was most frequently involved (11 patients in each group), basal ganglia (four in group I and six in group II), and midbrain (six in group I and one in group II). Group II patients had poorer recovery compared with group I. In group I, at the end of three months functional recovery was complete in 10, partial in two, and poor in three patients. In group II, four patients had complete, seven partial, and eight poor recovery.
Conclusion: JE results in a transient form of parkinsonian syndrome, which is associated with a lower frequency of tremor and prominent hypophonia. The presence of dystonia suggests more severe illness and poorer prognosis.
INTRODUCTION—This study was undertaken to evaluate the bone mineral density (BMD) in patients with complex regional pain syndrome type-I (CRPS-I) after stroke, and to correlate it with various clinical and neurophysiological parameters.
PATIENTS AND METHODS—Twenty patients with CRPS-I after stroke were included and a detailed neurological evaluation was carried out. The severity of CRPS-I was graded on the basis of shoulder hand syndrome score. All the patients underwent bone mineral densitometry of paralysed and non-paralysed forearm by dual energy x ray absorptiometry. The BMD of paralysed forearm was also compared with that of age matched healthy controls. Neurophysiological tests included sympathetic skin response in both upper and lower limbs and median somatosensory evoked potentials.
RESULTS—The mean age of patients was 57.2 (45-75) years and eight were females. Eight patients had severe weakness and 12 had moderate weakness of grade 2 on the hemiplegic side. There was significant reduction in BMD in the patients compared with controls (p<0.01). The bone density reduction correlated well with duration of illness (r = −0.673, p<0.01), shoulder hand syndrome score (r = −0.804, p<0.01), and Canadian neurological scale score (r = −0.738 p<0.01). Sympathetic skin response was not recordable bilaterally in all patients. Median somatosensory evoked potentials were not recordable in seven out of 20 patients who also had higher grade of CRPS-I.
CONCLUSION—Our results show significant reduction of BMD in patients with CRPS-I after stroke. The reduction in BMD correlates with the severity of shoulder hand syndrome score, degree of weakness, duration of hemiplegia, and the severity of stroke.
Keywords: stroke; complex regional pain syndrome type I; bone mineral density
INTRODUCTION—Data on single photon emission computed tomography (SPECT) in tuberculous meningitis are lacking and prompted this study. SPECT findings in tuberculous meningitis are reported and correlated with clinical and radiological findings.
PATIENTS AND METHODS—Seventeen patients with tuberculous meningitis that was diagnosed on clinical, radiological, and laboratory criteria have been included. Their age ranged between 5 and 62 years and four of them were female. Computed tomography and/or magnetic resonance imaging (MRI) and SPECT using 99mTc-ethylene cystine dimer were performed in all the patients. On the basis of Barthel index (BI) score the patients' outcome was defined as complete (BI = 20), partial (BI = 19-12), and poor recovery (BI<12).
RESULT—Eleven patients were in stage III and three each in stage II and stage I tuberculous meningitis. Two patients had hemiplegia and five quadriplegia. Computed tomography was abnormal in 11 out of 16 patients and revealed hydrocephalus in nine, basal exudates, infarction in subcortical white matter and basal ganglia in six patients each, frontal cortical infarction in one, and granulomata in three patients. Cranial MRI was carried out in four patients and revealed multiple granulomata, hydrocephalus, and brainstem infarction in two patients each. SPECT studies were abnormal in all except two patients and revealed hypoperfusion of the basal ganglia in 14, cortical hypoperfusion in 10, and midbrain hypoperfusion in one patient. At the three month follow up four patients had died, five had poor, three partial, and five complete recovery. The SPECT studies were more frequently abnormal compared with computed tomography but did not correlate with stage of meningitis or outcome.
CONCLUSION—In tuberculous meningitis subcortical and cortical hypoperfusion is common but it does not correlate with stage of meningitis or three month outcome.
Keywords: tuberculous meningitis; single photon emission computed tomography (SPECT); computed tomography; magnetic resonance imaging
OBJECTIVES—The role of
EEG and evoked potentials has not been evaluated in predicting the
prognosis of tuberculous (TB) meningitis. The present study was aimed
at evaluating the prognostic significance of clinical, radiological,
and neurophysiological variables using multi-variable analysis.
TB meningitis diagnosed on the basis of clinical, radiological, and CSF
criteria have been prospectively evaluated. All the patients were
subjected to a detailed neurological evaluation. The outcome was
defined 6 months after starting treatment on the basis of the Barthel
index (BI) score into poor (BI <12) and good recovery (BI⩾12). Death
was included in the poor recovery group for statistical analysis.
Thirteen clinical (age, sex, seizure, focal weakness, stage of
meningitis, Glasgow coma scale score, methyl prednisolone therapy), CT
(infarction, hydrocephalus, tuberculoma) and neurophysiological (EEG,
motor and somatosensory evoked potentials) variables were evaluated
employing single variable logistic regression followed by multivariable
logistic regression analysis. The best set of predictors were obtained
by stepdown logistic regression analysis.
patients were included in the present study. Their age ranged between 5 and 62 years, 11 were children younger than 12 years and 14 were
female. Nine patients were in stage I meningitis, 12 in stage II, and
33 in stage III. On single variable logistic regression analysis the
significant predictors of 6 months outcome of TB meningitis included
focal weakness, Glasgow coma scale (GCS), motor evoked potential (MEP)
and somatosensory evoked potential (SEP). On multivariable analysis the
best set of predictors comprised focal weakness, GCS, and SEP.
patients with TB meningitis focal weakness, GCS, and SEP are the best
predictors of 6 month outcome.
A case of acute transverse myelitis with severe postural hypotension is described.
The in vivo effects of xenoestrogens are of interest in relation to their potential health risks and/or beneficial effects on humans and animals. However, the apparent in vivo potency of the examined response can be confounded by a short half-life, and the metabolism of estrogens is very dependent on the nature of conversion and/or inactivation. To minimize such variables, we examined the estrogenic potency of a range of xenoestrogens in an acute in vivo assay--the stimulation of increased uterine vascular permeability in ovariectomized mice 4 hr after subcutaneous administration. While estradiol (E 2 ) and estriol (E 3 ; a relatively weak natural estrogen) readily induced vascular responses [median effective dose (ED 50 ) <10 -9 mol], much higher amounts of xenoestrogens were required. Bisphenol A was about 10,000-fold less potent than E 2 and E 3 , and octylphenol and nonylphenol were about 100,000-fold less potent; dioctyl phthalate, benzyl butyl phthalate, dibutyl phthalate, and trichlorinated biphenol produced no effect. Coumestrol was the most active phytoestrogen, with an ED 50 between 10 -6 and 10 -7 mol; genistein was about 10-fold less potent than coumestrol, and neither daidzein nor formononetin produced any marked effect, even at doses up to 10 -5 mol. All increases in vascular permeability could be blocked by the pure antiestrogen ICI 182,780. There was no evidence that any of the compounds could act as an antiestrogen in this assay or that they could exert synergistic effects in combination. These results indicate that even short-term exposure to most of the xenobiotic estrogens can induce typical estrogenic effects in vivo , but their estrogenic potency is very weak even when assessed in an acute response.
Six patients with Japanese encephalitis, four males and two females whose age ranged between 2 and 47 years, were subjected to neurophysiological and radiological studies. An EEG in five of the patients showed diffuse delta wave activity and one had an alpha coma. Delta activity seems to be due to thalamic involvement, which was seen on CT of two and MRI of all the patients. The thalamic lesions were characteristically bilateral and were haemorragic in five. Changes on MRI included abnormalities of the brainstem in three and the basal ganglia and spinal cord in one patient each. Lower motor neuron signs were present in three patients but abnormal MRI signals in the spinal cord were present in only one out of three patients in whom spinal MRI was carried out. Central motor conduction time in the upper limb was prolonged in three patients (five sides) and in the lower limbs in one (both sides), which was consistent with involvement of the cerebral cortex, thalamus, brainstem, and spinal cord. Changes in MRI and EEG in the acute stage may provide early diagnostic clues in patients with Japanese encephalitis.