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In preclinical studies, many stem cell/cellular interventions demonstrated robust regeneration and/or repair in case of SCI and were considered a promising therapeutic candidate. However, data from clinical studies are not robust. Despite lack of substantial evidence for the efficacy of these interventions in spinal cord injury (SCI), many clinics around the world offer them as “therapy.” These “clinics” claim efficacy through patient testimonials and self-advertisement without any scientific evidence to validate their claims. Thus, SCS established a panel of experts to review published preclinical studies, clinical studies and current global guidelines/regulations on usage of cellular transplants and make recommendations for their clinical use. The literature review and draft position statement was compiled and circulated among the panel and relevant suggestions incorporated to reach consensus. This was discussed and finalized in an open forum during the SCS Annual Meeting, ISSICON. Preclinical evidence suggests safety and clinical potency of cellular interventions after SCI. However, evidence from clinical studies consisted of mostly case reports or uncontrolled case series/studies. Data from animal studies cannot be generalized to human SCI with regard to toxicity prediction after auto/allograft transplantation. Currently, cellular/stem cell transplantation for human SCI is experimental and needs to be tested through a valid clinical trial program. It is not ethical to provide unproven transplantation as therapy with commercial implications. To stop the malpractice of marketing such “unproven therapies” to a vulnerable population, it is crucial that all countries unite to form common, well-defined regulations/legislation on their use in SCI. These slides can be retrieved from Electronic Supplementary Material.

Summary Background A systematic understanding of the burden of neurological disorders at the subnational level is not readily available for India. We present a comprehensive analysis of the disease burden and trends of neurological disorders at the state level in India. Methods Using all accessible data from multiple sources, we estimated the prevalence or incidence and disability-adjusted life-years (DALYs) for neurological disorders from 1990 to 2019 for all states of India as part of the Global Burden of Diseases, Injuries, and Risk Factors Study 2019. We assessed the contribution of each neurological disorder to deaths and DALYs in India in 2019, their trends in prevalence or incidence and DALY rates over time, and heterogeneity between the states of India. We also assessed the Pearson correlation coefficient between Socio-demographic Index (SDI) of the states and the prevalence or incidence and DALY rates of each neurological disorder. Additionally, we estimated the contribution of known risk factors to DALYs from neurological disorders. We calculated 95% uncertainty intervals (UIs) for the mean estimates. Findings The contribution of non-communicable neurological disorders to total DALYs in India doubled from 4·0% (95% UI 3·2–5·0) in 1990 to 8·2% (6·6–10·2) in 2019, and the contribution of injury-related neurological disorders increased from 0·2% (0·2–0·3) to 0·6% (0·5–0·7). Conversely, the contribution of communicable neurological disorders decreased from 4·1% (3·5–4·8) to 1·1% (0·9–1·5) during the same period. In 2019, the largest contributors to the total neurological disorder DALYs in India were stroke (37·9% [29·9–46·1]), headache disorders (17·5% [3·6–32·5]), epilepsy (11·3% [9·0–14·3]), cerebral palsy (5·7% [4·2–7·7]), and encephalitis (5·3% [3·7–8·9]). The crude DALY rate of several neurological disorders had considerable heterogeneity between the states in 2019, with the highest variation for tetanus (93·2 times), meningitis (8·3 times), and stroke (5·5 times). SDI of the states had a moderate significant negative correlation with communicable neurological disorder DALY rate and a moderate significant positive correlation with injury-related neurological disorder DALY rate in 2019. For most of the non-communicable neurological disorders, there was an increase in prevalence or incidence from 1990 to 2019. Substantial decreases were evident in the incidence and DALY rates of communicable neurological disorders during the same period. Migraine and multiple sclerosis were more prevalent among females than males and traumatic brain injuries were more common among males than females in 2019. Communicable diseases contributed to the majority of total neurological disorder DALYs in children younger than 5 years, and non-communicable neurological disorders were the highest contributor in all other age groups. In 2019, the leading risk factors contributing to DALYs due to non-communicable neurological disorders in India included high systolic blood pressure, air pollution, dietary risks, high fasting plasma glucose, and high body-mass index. For communicable disorders, the identified risk factors with modest contributions to DALYs were low birthweight and short gestation and air pollution. Interpretation The increasing contribution of non-communicable and injury-related neurological disorders to the overall disease burden in India, and the substantial state-level variation in the burden of many neurological disorders highlight the need for state-specific health system responses to address the gaps in neurology services related to awareness, early identification, treatment, and rehabilitation. Funding Bill & Melinda Gates Foundation; and Indian Council of Medical Research, Department of Health Research, Ministry of Health and Family Welfare, Government of India.

Thirty five floppy children seen during two year period, were subjected to clinical examination, electroneuromyography and muscle biopsy. The muscle biopsy was sent for routine histology, histochemistry and electron microscopy. Using muscle pathology as the 'gold standard' for diagnosis, the aetiological entities were spinal muscular atrophy (16), congenital muscular dystrophy (6), mitochondrial myopathy (3), congenital fibre type disproportion (2), acid mutase deficiency (1) and benign congenital hypotonia (6). Mental subnormality, seizures, ptosis and ophthalmoplegia suggested mitochondrial disease (n=2). Macroglossia, hepatomegaly and cardiomegaly along with the dive bomber effect on electromyography were useful clues to the diagnosis of Pompe's disease (n=1). Positive decremental test established the diagnosis of congenital myasthenia in one patient. Contrary to most previously published reports, infantile onset of spinal muscular atrophy did not always spell a poor prognosis on follow up. 'Floppy infant syndrome' has varied etiology. Comprehensive evaluation including clinical, electrophysiological and detailed histological examination is necessary for proper diagnosis and prognosis of this heterogenous entity.

Spinal muscular atrophy constitutes one of the major disease entities amongst infantile neuro-muscular disorders. On the basis of morphological evidence, it had been suggested that the infantile spinal muscular atrophy (ISMA) is due to maturation arrest of the myofibres at 20 weeks gestation. Therefore, in the present study morphological features of skeletal muscles from patients with ISMA was compared with foetal muscle obtained at different gestational ages (9-36 weeks, n=18). Of the 35 cases ofISMA, 22 were diagnosed as having SMA-I and 13 cases an SMA-II, characterised histologically by fascicles composed of groups of small, normal, intermediate sized and hypertrophic fibres. The former ones belonged to both histochemical fibre types, while the hypertrophic fibres in 21/35 cases were type I in nature. Redundant basal lamina was a predominant finding at ultrastructural level. Mature myotubes, a feature seen during foetal muscle development was not noticed in any of the cases of ISMA. Our observations suggest denervation atrophy to be the basic pathogenic mechanism rather than arrest in maturation. This was further supported by the changes seen in the spinal cord specimen of a 20 day old infant from a case of SMA I which revealed marked fallout of motor neurons in the anterior horn, chromatolysis and gliosis. Thus ISMA is a dynamic and progressive neurogenic atrophy secondary to degeneration and loss of spinal motor neurons possibly resulting in lack of trophic factors.

Introduction: Neurologists in their clinical practice are faced with inquiries about the suitability of stem cell approaches by patients with a variety of acute and chronic (namely neurodegenerative) disorders. The challenge is to provide these patients with accurate information about the scope of stem cell use as well as at the same time, empowering patients with the capacity to make an autonomous decision regarding the use of stem cells. Methods: The Indian Academy of Neurology commissioned an Expert Group Meeting to formulate an advisory to practicing neurologists to counsel patients seeking information and advice about stem cell approaches. Results and Conclusions: In the course of such counselling, it should be emphasized that the information provided by many lay websites might be unsubstantiated. Besides, standard recommendations for the stem cell research, in particular, the application of several layers of oversight should be strictly adhered in order to ensure safety and ethical use of stem cells in neurological disorders.

This article briefly outlines the proposed national epilepsy control program. The content of the article is based on four meetings held by invitation of the Ministry of Health. Invitees by ministry - Drs. D. C. Jain, M. Gourie Devi, V. Saxena, S. Jain, P. Satish. Chandra, M. Gupta, K. Bala, V. Puri, K. S. Anand, S. Gulati, S. Johri, P. S. Chandra, M. Behari, K. Radhakrishnan, D. Bachani. Presentations were made by Dr. M. Tripathi.The program will involve all neurologists across the country in teaching and training at state levels and a central monitoring committee.

While the past 2 decades have witnessed an increasing understanding of amyotrophic lateral sclerosis (ALS) arising from East Asia, particularly Japan, South Korea, Taiwan and China, knowledge of ALS throughout the whole of Asia remains limited. Asia represents >50% of the world population, making it host to the largest patient cohort of ALS. Furthermore, Asia represents a diverse population in terms of ethnic, social and cultural backgrounds. In this review, an overview is presented that covers what is currently known of ALS in Asia from basic epidemiology and genetic influences, through to disease characteristics including atypical phenotypes which manifest a predilection for Asians. With the recent establishment of the Pan-Asian Consortium for Treatment and Research in ALS to facilitate collaborations between clinicians and researchers across the region, it is anticipated that Asia and the Pacific will contribute to unravelling the uncertainties in ALS.

We have previously shown in our laboratory that cerebrospinal fluid from ALS patients (ALS-CSF) contains putative toxic factor(s). In the present study we determined the effect of ALS-CSF on the integrity of the Golgi apparatus of spinal motor neurons in the neonatal rats. CSF was injected intrathecally into three-day-old rat pups and subsequently the ultrastructural changes in the motor neurons were studied after 48 h, 1, 2 and 3 weeks. We observed that ALS-CSF causes fragmentation of the Golgi apparatus in a considerable number of motor neurons in the spinal cord. This was further confirmed when motor neurons were stained with an antibody against a medial Golgi protein (MG160). Thus, we suggest that the putative toxin(s) present in ALS-CSF may cause impairment in the protein processing leading to motor neuron death.

Setting: Tuberculous meningitis (TBM) has high mortality, especially in children. Early accurate diagnosis and adequate treatment would reduce this mortality. Diagnosis of TBM remains an enigma because of low cerebrospinal fluid (CSF) culture positivity for Mycobacterium tuberculosis and weak clinical correlation with conventional immunoassays. Objective: To evaluate significance of mycobacterial immune complexes (IgG) and anti-mycobacterial antibodies in the diagnosis of TBM. Method: CSF from TBM patients and various types of other neurological (both infectious and non-infectious) and non-neurological cases was studied for the presence of IgG and anti-mycobacterial antibodies using antigen capture (by anti-BCG) and multilayered ELISA (using M. tuberculosis soluble extract), respectively Results: IgG in CSF could be detected in 33 of 55 (60%) and anti-mycobacterial antibodies in 30 of 55 (55%) TBM cases. Presence of IgG, anti-mycobacterial antibodies or both could be detected in 45 of 55 (82%) of the TBM cases. Excepting three of the pyogenic meningitis CSF, none of the infectious (49), non-infectious neurological cases (30) and non-neurological controls (32) showed the presence of IgG or anti-mycobacterial antibodies. Conclusion: Detection of IgG along with anti-mycobacterial antibodies aids in diagnosis of a large proportion of TBM cases.

Publisher Summary Monomelic amyotrophy (MMA)—in which neurogenic atrophy is restricted to one limb—is a heterogeneous disorder, involving one upper or lower limb. Insidious onset of atrophy and weakness, presumed to be due to anterior horn cell involvement, starting in the second or third decade with male preponderance and sporadic occurrence are the characteristic features. Progression is slow and followed by stabilization within a few years, resulting in a benign outcome. The age of onset in the majority (90%) varies from 15 to 35 years with a median age of 20 years in MMA of the upper limb and slightly older in MMA of the lower limb with a median age of 25 years. In MMA of the upper limb, the common initial symptoms are weakness and atrophy in the majority, followed by tremulousnesss of the fingers. In various cases involving MMA of the lower limb, atrophy of the limb was noted by the patient due to pain while walking, and in nearly a third of the patients it was incidentally observed by a family member, friend, or physician during consultation for unrelated illness.

Previous studies from our laboratory suggest the presence of toxic factor(s) in the cerebrospinal fluid (CSF) of patients with amyotrophic lateral sclerosis (ALS) which induces degenerative changes in the spinal cord neurons. The present work was carried out to investigate the role of (-)-deprenyl in attenuating these degenerative changes. CSF samples from ALS and non-ALS neurological patients were injected into the spinal subarachnoid space of 3-day-old rat pups, followed by a single dose (0.01 mg/kg body weight) of (-)-deprenyl, administered 24 h after CSF injection. After a further period of 24 h, the rats were sacrificed and the spinal cord sections were stained with antibodies against phosphorylated neurofilament (NF, SMI-31 antibody) and glial fibrillary acidic protein (GFAP). Activity of lactate dehydrogenase (LDH) was also measured. (-)-Deprenyl injection resulted in a significant (61%) decrease in the number of SMI-31 stained neuronal soma in the ventral horn of the spinal cord of ALS CSF exposed rats. This was accompanied by a reduction in the astrocytes immunoreactive for GFAP. There was also a significant (35%) decrease in the LDH activity following (-)-deprenyl treatment. These results suggest that (-)-deprenyl may confer neuroprotection against the toxic factor(s) present in ALS CSF.

Monomelic amyotrophy of a single upper limb termed "brachial monomelic amyotrophy" (BMMA) is a benign lower motor neuron disorder in the young, with male preponderance, insidious onset of atrophy and weakness, electromyographic evidence of neurogenic pattern without conduction block, slow progression for 2-4 years followed by a stationary course. The aim of the study was to determine whether (i) atrophy and weakness in the affected limb progresses beyond 5 years; (ii) the illness spreads to the other limbs; and (iii) the disease progresses to amyotrophic lateral sclerosis.Forty-four patients who had a duration of illness of 5 years or more at the last follow-up examination were included in the study. Assessment of symptom profile, neurologic deficit and disability was performed at variable intervals during the follow-up period.Progression of the disease was seen in 37 (84.1%) patients, up to 5 years in 35 (79.5%), 6 years in one and 8 years in another patient. In seven patients (15.9%) the atrophy was accidentally noticed and no further change in the neurologic deficit was observed thereafter. Subsequent to attaining a stationary course, none of the 44 subjects developed fresh symptoms or signs during a mean follow-up period of 9.7 years (range 2.5-23). The mean duration of illness at last follow-up was 12.8 years (range 5-26.5) and in 22 (50%) subjects the disease duration was more than 10 years. Seven patients (15.9%) at presentation had minimal involvement of contralateral upper limb with gross asymmetry and later one more patient developed similar features. Thus, in only a small proportion (18.2%) of patients the neurologic deficit had extended beyond the confines of one upper limb. None of the patients developed involvement of cranial nerves, lower limbs or pyramidal signs.Progression of the neurologic deficit in the affected limb was seen up to 5 years in the majority followed by a stationary phase with no evidence of fresh neurologic deficit during the follow-up period. Spread to the contralateral upper limb with minimal neurologic deficit was seen in less than a fifth of the patients, but involvement of lower limbs was not observed. BMMA did not evolve to amyotrophic lateral sclerosis. These observations underscore the benign and self limiting course of BMMA.

Monomelic amyotrophy (MMA) a variant of motor neuron disease, has the characteristic features of wasting and weakness usually confined to a single upper or lower limb occurring predominantly in young males and a benign outcome. Symptoms of increased sweating, coldness and cyanosis have been observed in a few patients. The objective was to evaluate the involvement of the sympathetic nervous system in MMA by measuring sympathetic skin response.Electromyography, motor and sensory nerve conduction studies were done in all the four limbs of 9 patients with atrophy of one upper limb. Stimulation at Erb's point, and above and below elbow was done to look for evidence of conduction block. The sympathetic skin response (SSR) was recorded in all the limbs of these patients. Wasting and weakness of right upper limb in 7 patients and left upper limb in 2 patients was seen. The mean age was 28.3+/-10.1 years. Twenty-five age matched (24.8+/-4.8 years) healthy subjects served as controls.The mean SSR latency in the affected upper limbs of 9 patients was prolonged compared to the 25 control subjects (1.51+/-0.07 s vs 1.42+/-0.19 s, P=0.03). The mean value of SSR latency in 18 upper limbs of the 9 patients which included atrophied and unatrophied limbs was also prolonged compared to the controls (1.50+/-0.08 s vs 1.42+/-0.19 s, P=0.05). There was no significant difference of the mean latency of SSR between the atrophied upper limbs and the clinically normal upper limbs (1.51+/-0.07 s vs 1.49+/-0.09 s, P=0.51). The mean SSR latency in the lower limbs of the patients (2.09+/-0.09 s) did not significantly differ from the control subjects (1.97+/-0.28 s, P=0.09). Motor and sensory nerve conduction was normal and there was no evidence of conduction block.In MMA the sympathetic nervous system is involved in the atrophic upper limb and also in the clinically unaffected upper limb but not in the lower limbs.

One hundred patients (95 males, 5 females, mean age at presentation 31.6 +/- 9.4 yr) with various neurological disorders associated with HIV infection during 1989-1996 were evaluated at NIMHANS, Bangalore. Eighty patients belonged to group I associated with opportunistic neuroinfections and 20 to group II--non infectious neurological disorders. Cryptococcal meningitis either alone (n = 31) or associated with tuberculous meningitis (n = 6) was the most common (46.3%) followed by neurotuberculosis either alone (n = 24) or with cerebral toxoplasmosis (n = 4) accounting for 35 per cent. Other opportunistic neuroinfections included cerebral toxoplasmosis, herpes zoster, fulminant pyogenic meningitis and neurosyphilis. Clinical characteristics, diagnostic clues, their laboratory and radiological profiles and problems encountered in diagnosis and management of these opportunistic infections are highlighted. In group II (19 males and one female; mean age of 32.6 +/- 9.4 yr), two patients had cortical dementia, three acute brain stem involvement, two epilepsy and one had features suggestive of progressive multifocal leukoencephalopathy. Two patients of group I during follow up developed cortical dementia. Six had peripheral nervous system involvement similar to Guillain-Barre syndrome. Sixty six patients (63 of group I and 3 of group II) progressed to AIDS, 33 patients from group I and one patient from group II succumbed to the disease. With the rapid increase in the incidence of HIV/AIDS and an increase in the neurological manifestations of HIV/AIDS it is important to recognise the magnitude of the problem for health planning in India.

Clinical, histological, immunohistochemical and ultrastructural features of 5 cases of inclusion body myositis -4 sporadic (s-IBM) and one hereditary (h-IBM) form are described. These patients (3 men, 2 women) had chronic progressive weakness of varying severity in all 4 extremities with sparing of cranial muscles. Elevation of CPK was noted in 2 patients. Electromyography revealed features of myopathy in 4 and additional neurogenic changes in 2 subjects. Clinical diagnosis was often other than inclusion body myositis. Presence of characteristic eosinophilic inclusions within the vacuoles established the diagnosis. The inclusions were congophilic and showed positivity to ubiquitin, beta-amyloid and SMI-31 in the sporadic cases while congophila was absent in the hereditary form. Immunostaining to hyperphosphorylated-tau was negative in both s-IBM and h-IBM. Membraneous whorls were observed at ultrastructural level. None of the patients improved with steroids and trial with other immunosuppressants was unsuccessful.

The anaesthetic management of children with neuromuscular diseases giving rise to hypotonia is associated with a variety of problems. Ketamine alone was given by the intravenous or intramuscular route to 32 children with Floppy Infant Syndrome for diagnostic muscle biopsy. The patients aged between three months and 12 yr and weighing 3.2 to 28 kg were studied over three years (1986-1988). The special anaesthetic problems are discussed. The use of ketamine dissociative anaesthesia is reviewed with emphasis on congenital neuromuscular disorders.

The molecular genetic analyses (PCR and Southern hybridization) of Indian patients with myotonic dystrophy (DM) were carried out to determine the degree of repeat expansion and an attempt was made to correlate the repeat number with disease severity. A scoring system based on the salient clinical features was devised to objectively assess the disease severity. The repeat expansion was seen in 11 of 12 patients examined and showed an inverse correlation with the age of onset confirming the phenomenon of anticipation. This was further established in the two pedigrees studied, clearly demonstrating both clinical and genetic anticipation. The clinical severity score, however, did not correlate well with the repeat number. Nonetheless, such molecular genetic analyses may have immense value as a screening procedure to identify premutations as well as in prenatal diagnoses.

To investigate the prognostic role of tumour necrosis factor (TNF) in Japanese encephalitis virus (JEV) infection, we measured the immunoreactive forms of TNF concentrations in the serum and cerebrospinal fluid (CSF) of 47 laboratory-confirmed cases of JE. It was observed that TNF levels were elevated (15 pgm/ml) in all the 47 serum samples (range 19.4-923.8 pg/ml), while in 46/47 CSF samples TNF was elevated (range 10.8-376 pg/ml). The mean (SD) TNF levels in the serum of fatal cases was 234.34 pg/ml (304.40) as compared to the mean of 85.31 pg/ml (SD 153.92) in nonfatal cases. Similar observations were also made with respect to the TNF levels in the CSF; the mean of fatal cases was 69.39 pg/ ml (SD 39.00) in contrast to the mean of 62.41 pg/ml (SD 75.25) of nonfatal cases. The increase in TNF levels did not show any correlation to the duration of illness. It was further observed that the mortality rate increased with increasing concentrations of TNF in the serum and CSF. Correlation of laboratory parameters to final outcome revealed that TNF concentrations above 50 pg/ ml in serum correlated significantly (P = .05) with a fatal outcome, whilst high levels of JEV-IgM antibodies (500 units) in the CSF correlated with a nonfatal outcome (P = .03). These results suggest that TNF can be used as a possible prognosticator of a fatal outcome in JEV infection.

One of the adjunctive modes of diagnosing tuberculous meningitis (TBM) is to detect immune responses in the cerebrospinal fluid (CSF) to the Mycobacterium tuberculosis antigen. Up to 70% of clinical TBM reveal the presence of antimycobacterial antibody by the enzyme-linked immunosorbant assay. Defining the specificity of this immune response by Western blotting on separated M. tuberculosis antigen has been attempted in this study. Only antimycobacterial antibody-positive TBM cases were included in the study. An analysis of 30 such TBM cases showed a major immune reactivity to the 30- to 40-kDa region (93%) while a lower degree of immune reactivity was seen to the 14-kDa region (87%) and to the 18- to 25-kDa region (60%). Grossly the antibody reactivity on Western blot correlated with the ELISA results. Assessment of antimycobacterial antibody in the neurologic control CSF samples of pyogenic meningitis [n = 10], cryptococcal meningitis [6], neurocysticercosis [28], neurosyphilis [8], viral meningoencephalitis [8], carcinomatous meningitis [8], iatrogenic meningitis [6], and nonneurological control CSF samples from patients undergoing spinal anesthesia [20] revealed the presence of antibody in the CSF of 2 of the 10 pyogenic meningitis and 5 of the 28 neurocysticercosis cases. A Western blot analysis of these 7 cases revealed immune reactivity to 30- to 40-kDa regions only in 2 cases (1 of pyogenic and 1 of neurocysticercosis). The remaining 5 CSF samples did not reveal any immune reactivity on Western blotting, although ELISA demonstrated antimycobacterial antibodies. The antibody response to M. tuberculosis lipoarabinomannan and 38-kDa antigen by ELISA revealed 70.58 and 41.17% positivity, respectively. Thus this study has demonstrated that, by Western blotting, the major immune response is to the 30- to 40-kDa region, namely, lipoarabinomannan. Further, this finding will be useful for specific immunodiagnosis of the TBM.

A feasibility study was conducted in an urban population of 3,040 in Bangalore, South India, to understand the baseline characteristics, evaluate screening questionnaires, identify potential problems and determine the magnitude of the problems. The target population was selected by a random method, from four census enumeration blocks of a specific urban area. A two-phase study design was adopted consisting of screening by trained field investigators in the initial stage and clinical examination by a neurologist in the second stage. The information was collected by an interview method on a house-to-house basis. Evaluation of the screening instruments yielded high sensitivity and specificity rates, and it became clear that there is a need to reduce false-positive results in the screening questionnaire for individuals above 7 years of age. The prevalence of neurological disorders was 32.8 per 1,000 population (with a rate of 7.8/1,000 for epilepsy). It appears feasible to detect a wide range of neurological disorders using the methods described.

Tuberculous meningitis (TBM) is a serious meningitic infection commonly found to occur in the developing countries endemic to tuberculosis. Based on the clinical features alone, the diagnosis of TBM can neither be made nor excluded with certainty. Unfortunately there is still no single diagnostic method that is both sufficiently rapid and sensitive. Most factors found to correlate with poor outcome can be directly traced to the stage of the disease at the time of diagnosis. The only way to reduce the mortality and morbidity is by early diagnosis and timely recognition of complications and institution of the appropriate treatment strategies.

From 1977 through 1981, we examined 23 patients with single-limb atrophy. Thirteen had upper-limb and ten had lower-limb involvement. The characteristic clinical features were insidious onset in the second and third decades, male preponderance, sporadic occurrence, wasting and weakness confined to one limb, and absence of involvement of the cranial nerves, cerebrum, brain stem, and sensory system. The electromyographic features, along with histologic features of neurogenic atrophy, were suggestive of an anterior horn cell lesion. The slow progression of illness for two to four years followed by a stationary phase was observed. There was no clinical evidence of involvement of the other three limbs even in patients with long-standing illness of ten to 15 years' duration.