Sequential carotid Doppler study in acute stroke and its clinical correlation: A prospective study.

Objectives: Resistive index (RI) and pulsatility index (PI) assessed on carotid Doppler assess the hemodynamic status of cranial vasculature. They are related to the severity of stroke and help determine the overall outcome. This study was done to compare the hospital stay and stroke severity with RI and PI of both internal carotid arteries. Materials and Methods: Patients >18 years of age presenting within 48 h of anterior circulation stroke (either ischemic or hemorrhagic) were included. They were divided into two groups based on their length of stay (LOS). They were assessed clinically on days 1, 3, and 5, and underwent a carotid Doppler study on the same days. The Doppler parameters were correlated with the LOS and stroke severity for possible associations. Results: One hundred and one patients were included. Forty-seven patients had a favorable outcome based on LOS. In this group, significant decrease in RI and PI scores was seen from days 1 to 3. In patients with unfavorable outcome, there was a significant increase in PI on days 1-3 and days 1-5. The National Institutes of Health Stroke Scale decreased significantly from days 1 to 5 in favorable group. Conclusion: For those with an unfavorable outcome and prolonged LOS, PI continues to increase suggesting a failure of autoregulation. Carotid Doppler can be a simple bedside tool to predict outcome in patients with acute stroke.

Autonomic Function Tests, Heart Rate Variability, and Electrophysiological Evaluation in Patients With a Primary Episodic Headache: An Observational Study.

PURPOSE: Cranial autonomic symptoms are typically associated with the trigeminal autonomic cephalalgias and also present in substantial cases of migraine. Autonomic nervous system dysfunctions are also been reported in headache disorders and postulated to promote headache attacks. This study was aimed to evaluate the parasympathetic and sympathetic autonomic functions tests in patients with a episodic primary headache and to investigate, if any, electrophysiological abnormalities in the blink reflex test and sympathetic skin response test in these patients. METHODS: In this cross-sectional study, a total of 100 patients, 50 patients each of migraine and tension-type headache attending the neurology OPD and fulfilling the diagnostic criteria of headache disorders were enrolled. Autonomic functions tests were performed in the Department of Physiology, whereas electrophysiological tests were powered by the Editorial Manager and ProduXion Manager from Aries Systems Corporation performed in the Department of Neurology. RESULTS: Significant association ( P < 0.05) was observed in "blood pressure response to sustained handgrip" (sympathetic activity) and "heart rate response to Valsalva maneuver" (parasympathetic activity) among patients with migraine. Although the mean sympathetic skin response latency of patients with migraine was within the normal range, it was significantly prolonged in comparison with the control group. "Blood pressure response to sustained handgrip" and "heart rate variability" were found to be significantly ( P < 0.05) different in patients with a tension-type headache. The blink reflex test was observed to be normal in all patients with a headache. Patients with migraine showed a significant dysautonomia in category three of the Ewing battery for autonomic functional disability. CONCLUSIONS: Autonomic functional abnormality, both sympathetic and parasympathetic, does exist in patients with a primary episodic headache.

Cranial Autonomic Symptoms in Migraine: An Observational Study.

Objective: Our aim was to observe frequency of cranial autonomic symptoms (CAS) in migraineurs (primary) and its relation with laterality of headache or other factors, if any. Background: Migraine episodes have headaches with or without aura, and sometimes associated with systemic autonomic nervous system symptoms. Primarily presence of cranial autonomic symptoms suggests diagnosis of TACs. But many studies reported cranial autonomic symptoms (CAS) ranging from 26% to 80% in migraine patients. Material and Methods: Consecutive patients of migraine attending our headache clinic were included in our study. Presence of CAS was recorded with respect to ocular, nasal, facial and aural symptoms along with headache characteristics and laterality information. Detailed clinical examination was performed. We used ICHD 3 (beta version) criteria. Results: Our study cohort comprised of 200 patients having mean (± SD) age 31.12 (± 10.67) years. There were 157 (78.5%), females. Out of 200 patients, 148 (74%) were having at least one CAS, of which 70% were having 2 or more CAS. Frequency of CAS was lacrimation (45.5%), conjunctival injection (34.5%), eyelid edema (34%), aural fullness (27.5%), facial sweating (25%), facial flushing (17.5%), nasal congestion (9%), rhinorrhea (5%) and ptosis (4%). Bilateral CAS was present in 129 (87%) and unilateral CAS in 19 (13%) (OR 35.31; 95% CI 9.19 to 135.7), (P < 0.0001). Sunlight as a trigger was present in all 148 (100%) patients. Conclusion: Our study showed that CASs in migraine is common and bilateral. Sunlight triggers headache in almost all CAS positive patients.

A Comparative Study of Regional Cerebral Blood Flow Asymmetry Index in Stroke Patients with or without Poststroke Depression Using 99m Tc-ECD Single-Photon Emission Computed Tomography.

Introduction Stroke is a major cause of death and disability around the globe. The development of depression following a stroke further increases the disability and impairs functional recovery. In recent decades, despite the advancement in structural and nuclear medicine imaging, the pathophysiologic basis of poststroke depression (PSD) is not well understood. Etiopathogenesis of PSD is multifactorial and afflictions of the frontal lobe, hippocampus, limbic region, and basal ganglia projections are implicated. Aim The aim of this study was to assess the regional cerebral blood flow (rCBF) using 99m Tc-ethyl cysteinate dimer single-photon emission computed tomography (SPECT) in patients with (PSD + ) or without PSD (PSD-). Materials and Methods To evaluate the hemispheric asymmetry, the percentage of asymmetry index (AI) was calculated for frontal, temporal, parietal, occipital, putamen, caudate, and thalamic regions of brain and compared between PSD+ and PSD-. The correlation between AIs over the different brain regions was also established in patients of PSD+ and PSD-. Our study cohort included 122 patients between 6 weeks and 1 year of stroke. Depression was present in 52 (42.6%) patients, assessed by hospital anxiety and depression scale (HADS) and general health questionnaire-28 items (GHQ-28) scale. The 28 patients with PSD+ and 18 PSD- gave consent for SPECT study. Results Our results are based on 46 patients who underwent SPECT study. In patients with PSD+ and PSD-, the HADS and GHQ-28 scores were 8.93 ± 2.77 vs. 3.94 ± 2.15 ( p = 0.001) and 40.96 ± 9.48 vs. 17.72 ± 5.38 ( p = 0.001), respectively. A significant difference in rCBF AI was found in the temporal lobe ( p = 0.03) between patients of PSD+ and PSD-. On logistic regression analysis, the odds ratio of rCBF AI for temporal lobe was 0.89 (95% confidence interval [CI]: 0.80-0.99; p = 0.04) and caudate nucleus was 0.85 (95% CI: 0.73-0.98; p = 0.03), which were statistically significant. PSD correlated with AI in temporal region ( r = -0.03; p = 0.03) but did not show significant correlation with other regions of brain between PSD+ and PSD-. Conclusion The presence of temporal lobe rCBF AI on SPECT is significantly associated with PSD. This may reflect the dysfunction of the limbic system and contribute to the occurrence of PSD.

Expanding the Clinical Spectrum of RFC1 Gene Mutations.

Biallelic intronic repeat expansion in the replication factor complex unit 1 (RFC1) gene has recently been described as a cause of late onset ataxia with degeneration of the cerebellum, sensory pathways and the vestibular apparatus. This condition is termed cerebellar ataxia, neuropathy, and vestibular areflexia syndrome (CANVAS). Since the identification of this novel gene mutation, the phenotypic spectrum of RFC1 mutations continues to expand and includes not only CANVAS but also slowly progressive cerebellar ataxia, ataxia with chronic cough (ACC), isolated sensory neuropathy and multisystemic diseases. We present a patient with a genetically confirmed intronic repeat expansion in the RFC1 gene with a symptom complex not described previously.

Optimizing the selection of Parkinson's disease patients for neuromodulation using the levodopa challenge test.

BACKGROUND: In Parkinson's disease (PD), early stages are associated with a good long-duration response and as the disease advances, the short-duration response predominates. The transition between the long-duration and short-duration responses may be an important and measurable intermediate stage. A critical criterion in determining the candidature for neuromodulation is a beneficial response to an 'off-on' levodopa challenge test. This test is usually reserved for those that have already developed marked short-duration response and are candidates for deep brain stimulation (DBS) surgery. However, identifying those that are in transition may allow DBS to be offered earlier. OBJECTIVE: The objective of the study was to determine if the transition from a long-duration to a short-duration response can be assessed on a levodopa challenge test. METHODS: An 'off-on" levodopa challenge test was done in sixty-five PD patients divided into four groups based on the disease duration. RESULTS: OFF motor scores increased in all groups [Mean ± STD; 22.94 ± 8.52, 31.53 ± 9.87, 34.05 ± 9.50, and 33.92 ± 10.15 in groups 1-4, respectively] while a significant response to medication was maintained on 'off-on' testing. The mean levodopa equivalency dose in groups 1 and 2 was significantly less than in groups 3 and 4. This transition occurred between years 7 and 9 of disease duration. CONCLUSION: Performing a regular levodopa challenge test, when levodopa dose increases substantially, should be considered to determine the ideal time for DBS in patients with Parkinson's disease.

Mercury and Movement Disorders: The Toxic Legacy Continues.

Mercury (Hg) exists in the environment as inorganic (metallic Hg vapor, mercurous and mercuric salts) or organic (bonded to a structure containing carbon atoms) forms. Neurotoxic effect of Hg is known for years. While the organic form (methylmercury (meHg)) led to the Minamata incidence in Japan and "wonder-wheat" disaster in Iraq, the "mad hatters" and "Danbury shakes" were related to the inorganic elemental form (Hg vapor). Human exposure to toxic Hg continues in the modern world to a large extent by artisanal gold mining, biomass combustion, chloralkali production, and indigenous medicine use to name a few. Heavy industrial use of Hg contaminates air and landfills, affecting the aquatic ecosystem and marine food chain. A detailed social and occupational history with a high index of clinical suspicion is required to not miss this toxic etiology for movement disorders like ataxia, tremor, or myoclonus. In this review, we have discussed the past and present global health impact of Hg from a movement disorder perspective. The connection of Hg with neurodegeneration and autoimmunity has been highlighted. We have also discussed the role of chelating agents and the preventive strategies to combat the neurotoxic effects of Hg in the modern world.

Manganese and Movement Disorders: A Review.

Scientific and technological advances achieved with industrial expansion have led to an ever-increasing demand for heavy metals. This demand has, in turn, led to increased contamination of soil, water and air with these metals. Chronic exposure to metals may be detrimental not only to occupational workers but also to the nonoccupational population exposed to these metals. Manganese (Mn), a commonly used heavy metal, is an essential cofactor for many enzymatic processes that drive biological functions. However, it is also a potential source of neurotoxicity, particularly in the field of movement disorders. The typical manifestation of Mn overexposure is parkinsonism, which may be difficult to differentiate from the more common idiopathic Parkinson's disease. In addition to environmental exposure to Mn, other potential etiologies causing hypermanganesemia include systemic health conditions, total parenteral nutrition and genetic mutations causing Mn dyshomeostasis. In this review, we critically analyze Mn and discuss its sources of exposure, pathophysiology and clinical manifestations. We have highlighted the global public health impact of Mn and emphasize that movement disorder specialists should record a detailed social and occupational history to ensure that a toxic etiology is not misdiagnosed as a neurodegenerative disease. In the absence of a definite therapeutic option, early diagnosis and timely institution of preventive measures are the keys to managing its toxic effects.

Muscle Tone Physiology and Abnormalities.

The simple definition of tone as the resistance to passive stretch is physiologically a complex interlaced network encompassing neural circuits in the brain, spinal cord, and muscle spindle. Disorders of muscle tone can arise from dysfunction in these pathways and manifest as hypertonia or hypotonia. The loss of supraspinal control mechanisms gives rise to hypertonia, resulting in spasticity or rigidity. On the other hand, dystonia and paratonia also manifest as abnormalities of muscle tone, but arise more due to the network dysfunction between the basal ganglia and the thalamo-cerebello-cortical connections. In this review, we have discussed the normal homeostatic mechanisms maintaining tone and the pathophysiology of spasticity and rigidity with its anatomical correlates. Thereafter, we have also highlighted the phenomenon of network dysfunction, cortical disinhibition, and neuroplastic alterations giving rise to dystonia and paratonia.

Iron Chelation in Movement Disorders: Logical or Ironical.

Iron is probably as old as the universe itself and is essential for sustaining biological processes. The remarkable property of iron complexes to facilitate electron transfer makes it a significant component of redox reactions that drive the essential steps in nucleic acid biosynthesis and cellular functions. This, however, also generates potentially harmful hydroxyl radicals causing cell damage. In the movement disorder world, iron accumulation is well known to occur in neurodegeneration with brain iron accumulation, while dysfunctional iron homeostasis has been linked with neurodegenerative diseases like Parkinson's disease and Huntington's disease to name a few. Targeting excess iron in these patients with chelation therapy has been attempted over the last few decades, though the results have not been that promising. In this review, we have discussed iron, its metabolism, and proposed mechanisms causing movement disorder abnormalities. We have reviewed the available literature on attempts to treat these movement disorders with chelation therapy. Finally, based on our understanding of the pathogenic role of iron, we have critically analyzed the limitations of chelation therapy in the current scenario and the various unmet needs that should be addressed for selecting the patient population amenable to this therapy.

Clinical value of perilesional perfusion deficit measured by Technetium-99m-ECD single-photon emission computed tomography in hypertensive intracerebral hemorrhage.

Pathological and experimental studies indicate the existence of a "penumbra" of progressive tissue damage and edema in regions immediately surrounding a hematoma in patients of intracerebral hemorrhage (ICH). This zone of oligemia surrounding ICH has a potential for perfusion recovery. Improved understanding of the pathophysiology of perilesional blood flow changes and brain injury after ICH may result in improved treatment strategies. The aim was to study perilesional blood flow changes in ICH by perfusion deficit (PD) measured by single-photon emission computed tomography (SPECT) and to correlate it with the severity of ICH and outcome. Forty-four patients of computed tomography (CT) documented nonlobar deep ICH suggestive of hypertensive hematoma of <7 days duration were subjected to 99mTc-ethylene diacetate SPECT scans of the brain. Patients with significant midline shift (0.5 cm) or global blood flow reduction were excluded from the analysis. SPECT scan of the brain was analyzed by segmental analysis, a semi-quantitative method of cerebral blood flow. A difference of radiotracer uptake of >10% between the region of interest of ICH cases and the ratio between the two ROI below 0.9 was taken as a significant PD. A correlation of PD was analyzed with that of various parameters such as the severity of stroke, duration from onset of ictus, and imaging including CT scan of the brain and SPECT scan. A statistically significant difference in the percentage of radiotracer uptake on comparison of ipsilateral and contralateral to ICH (P < 0.001) was observed, suggesting a significant hypoperfusion in the perilesional area in patients with ICH. A statistically significant correlation was noted between the severity of stroke and PD indicated by various parameters such as the National Institutes of Health Stroke Scale (NIHSS) score at admission (r = 0.328, P = 0.016), Glasgow Coma Scale (GCS) score at admission (r = -0.388, P = 0.005), and ICH score at admission (r = 0.314, P = 0.020). This study demonstrated more severe hypoperfusion in clinically severe ICH which is a possible explanation of poor outcomes in severe ICH cases. We observed hypoperfusion on SPECT study in 25 of 34 (73.5%) patients with subacute ICH and 5 of 10 patients (50%) with acute ICH. The mean time from the onset of ictus to SPECT scan done was 5.04 ± 1.75 days with a range of 1-7 days, suggesting the persistence of hypoperfusion in subacute stages too. This finding may be of clinical importance for identifying the salvageable area surrounding ICH for any possible intervention in future to improve the outcome. This study demonstrates that perilesional PD occurs in acute and subacute cases of ICH. This hypoperfusion is possibly time related and appears to be more severe in patients having major ICH with poor clinical and imaging parameters. This area of hypoperfusion or ischemic penumbra is a potential site for perfusion recovery to improve clinical outcomes and to reduce long-term neurological deficits.

Diagnosing Muscular Dystrophies: Comparison of Techniques and Their Cost Effectiveness: A Multi-institutional Study.

Background The diagnosis of muscular dystrophies involves clinical discretion substantiated by dystrophic changes on muscle biopsy. The different subtypes of muscular dystrophy can be diagnosed using techniques to identify the loss of protein or molecular alterations. Materials and Methods Clinically suspicious cases confirmed to have muscular dystrophy on muscle biopsy seen at two tertiary care centers in North India were enrolled for the study. Immunohistochemistry (IHC) for dystrophin, merosin, sarcoglycan, emerin, and dysferlin proteins was performed. The spectrum of muscular dystrophies diagnosed was analyzed. Cost of diagnosing the cases using IHC was estimated and compared with that of standard molecular tests available for the diagnosis of muscular dystrophies. Statistics Descriptive statistics were used for data analysis. Mean and standard deviations were used for continuous variables, whereas categorical variables were analyzed using frequency percentage. Results A total of 47 cases of muscular dystrophies were studied. This included nine cases of Duchenne, three cases of Becker's dystrophy, and one dystrophinopathy carrier. One case of α, seven cases of ß, and two cases of δ sarcoglycanopathy, along with two cases of facioscapulohumeral dystrophy and a single case of dysferlinopathy were detected. Genetic studies were required for a subset of 16 cases. The cost of using muscle biopsy and IHC was substantially lower than that of molecular methods for the identification of muscular dystrophy subtypes. Conclusion We detailed an algorithmic approach for diagnosing muscular dystrophies using muscle biopsy. The prevalence of biopsy proven muscular dystrophies from two tertiary care centers in North India is compared with that from other centers. Genetic studies are currently of limited availability in India and are more expensive as compared with biopsy and IHC. Using these methodologies sequentially with a "biopsy first approach" may be the prudent approach for low-income countries.

Managing autonomic dysfunction in Parkinson's disease: a review of emerging drugs.

Introduction: Autonomic dysfunction is an integral part of Parkinson disease (PD) complex and can be seen both in early and advanced stages. There is a paucity of medicines available to manage autonomic dysfunction in PD and this adds to the considerable morbidity associated with the illness.Areas covered: The pathophysiology and the available therapeutic options of autonomic dysfunction seen in PD are discussed in detail. The potential targets for novel regimens are reviewed and the available literature on the drugs emerging in management of autonomic dysfunction in PD is highlighted.Expert opinion: In the current scenario, there are several drugs that can be tried for constipation viz stool laxatives, prucalopride, prokinetic agents and a high fiber diet. Bladder dysfunction has been treated with ß-agonists and with mirabegron, a selective ß-3 agonist, the anticholinergic side effects are minimized, and the drug has been found to be effective. Orthostatic hypotension is managed with midodrine while droxidopa is a new drug with promising efficacy. Botulinum toxin works best for management of sialorrhea, but repeated injections are needed.

A 2 DS 2 Score to Predict the Risk of Stroke-Associated Pneumonia in Acute Stroke: An Indian Perspective.

Background Stroke-associated pneumonia (SAP) is an important cause of poststroke morbidity and mortality. Several clinical risk scores predict the risk of SAP. In this study, we used the A 2 DS 2 score (age, atrial fibrillation, dysphagia, sex, and stroke severity) to assess the risk of SAP in patients admitted with acute stroke. Methods A high (5-10) and a low (0-4) A 2 DS 2 score was assigned to patients with acute stroke admitted to the neurology ward. Univariate binary logistic regression analysis was performed to find the strength of association of SAP and A 2 DS 2 score. Results There were 250 patients with acute stroke of which 46 developed SAP. Forty-four patients developed SAP in high score as against 2 in low-score group (odds ratio [OR] = 0.03, 95% confidence interval [CI] = 0.01-0.15, p = 0.0001). A 2 DS 2 score >5 had sensitivity of 82.6% and specificity of 65.1% to predict SAP. The mean A 2 DS 2 score in patients with pneumonia was 7.02 ± 1.40 compared to 4.75 ± 1.92 in patients without pneumonia ( p = 0.0001). Conclusions A 2 DS 2 score has a high sensitivity of 82% in predicting the risk of SAP and is a useful tool to monitor patients after acute stroke. A 2 DS 2 score can help in timely detection and prevention of SAP and reduction in caregiver's burden.

Mandating nerve biopsy: A step towards personalizing therapy in pure neuritic leprosy.

Pure neuritic leprosy (PNL) accounts for 5% to 10% of leprosy patients who usually present with asymmetrical neuropathy in the absence of lepra bacilli on slit-skin smears. However, nerve biopsies in PNL lack appropriate categorization in current immunologic terms. We aimed to classify nerve biopsies according to the immune spectrum of leprosy and assess the role of histologic classification of nerve biopsies in treating PNL. Patients from two tertiary care referral centres were enrolled in this incident case study. Patients presenting with mononeuropathy and multiple mononeuropathies presumably with leprosy, without skin lesions, underwent nerve biopsy and slit-skin smear examination. Amongst 78 patients with mononeuropathy, 38 were diagnosed with leprosy on nerve biopsy. Leprosy was classified as tuberculoid in 16, lepromatous in 5 and borderline in 17 patients. Lepra bacilli were present in 15 biopsies. On comparing histologic subtypes with number of nerves involved clinically, a significant number of cases with single nerve involvement showed multibacillary (BB, BL or LL) histology and vice versa. Nerve biopsy helps in diagnosing patients presenting with PNL and aids in classifying it to customize the treatment for best results. Current treatment recommendations for PNL from WHO and National Leprosy Eradication Program are based on clinical assessment only, which are likely to result in inconsistent treatment and possibly relapse in cases where histomorphology shows disparity. Inclusion of nerve biopsy to guide therapy in patients with PNL is suggested.

Dopa-responsive Dystonia in a Child Misdiagnosed as Cerebral Palsy.

Dopa-responsive dystonia also known as "Segawa's syndrome" was first described in 1976. The dystonia typically shows diurnal variations and is more marked toward the end of the day and improves in sleep. This entity is often misdiagnosed in the clinical setting, mostly due to the lack of awareness, and these patients are exposed to various treatment regimens and nonpharmacological measures. We present a boy being treated as dystonic cerebral palsy who showed significant improvement in dystonic symptoms with L-dopa therapy.

Evaluation of polymerase chain reaction in nerve biopsy specimens of patients with Hansen's disease.

BACKGROUND: Pure neuritic variety of leprosy (PNL) presents as peripheral neuropathy with absent skin lesions and negative skin smears. Diagnosing PNL is an uphill task as most of these patients have nonspecific changes on nerve biopsy. In such circumstances, additional molecular diagnostic tools like polymerase chain reaction (PCR) has proven to be useful in diagnosing leprosy. The present study was planned to evaluate the role of PCR in nerve biopsy specimens of patients with PNL. METHODS: Patients attending the neuromuscular clinic from January 2013 to June 2014 with mononeuropathy multiplex underwent detailed diagnostic evaluation to ascertain the cause of neuropathy. Patients where this evaluation failed to establish an etiology underwent a nerve biopsy. RESULTS: Nerve biopsy was done in 52 patients, of which 35 were diagnosed as pure neuritic leprosy. Definite leprosy with positive wade fite staining for lepra bacilli was seen in 13 patients and 22 biopsies revealed a probable leprosy without lepra bacilli being identified. PCR for M. leprae was positive in 22 patients (62%). 12 of the 13 cases with definite leprosy on histopathology were PCR positive while in the AFB negative group, PCR was positive in 10 cases. PCR had a sensitivity of 92.3%, specificity of 54.5%. The positive and negative predictive value of PCR was 54.5% and 92.3% respectively. CONCLUSIONS: PCR helps in diagnosing PNL in doubtful cases. A positive PCR increases the sensitivity of detection of M. leprae especially in cases of probable PNL group where AFB cannot be demonstrated on histopathology.

Stroke Associated With Varicella Zoster Vasculopathy: A Clinicoradiological Profile of 3 Patients.

INTRODUCTION: Varicella zoster (VZ) vasculopathy is a rare but well recognized cause of stroke. In the absence of zoster rash and infection in remote past, the disease can pose diagnostic challenge. We report 3 cases of anterior circulation stroke occurring in close temporal relation to VZ. Their clinical, radiologic, and angiographic features are discussed. CASE REPORT: Of the 3 patients, 2 had stroke within a span of 4 to 6 weeks of herpes zoster ophthalmicus while the third patient had zoster of cervical dermatome. Magnetic resonance imaging revealed acute subcortical infarcts in 2, while 1 patient showed acute on chronic infarct in left middle cerebral artery territory. The magnetic resonance angiography was abnormal in 2 patients while it was normal in third. All the patients were treated with acyclovir and antiplatelets with good recovery in 2. CONCLUSIONS: VZ associated vasculopathy may have diverse clinical profile and neuroimaging features. It should be considered as an important and treatable cause of stroke in appropriate clinical settings.

Nerve biopsy in Indian patients with mononeuropathy multiplex of undetermined etiology.

INTRODUCTION: A diagnosis of mononeuropathy multiplex (MM) requires detailed evaluation to determine etiology. We performed nerve biopsy on patients with MM in whom the etiology could not be established via other investigations. METHODS: Sixty-eight patients with MM seen between January 2013 and June 2014 underwent detailed diagnostic evaluation. Those in whom the investigations failed to establish an etiology underwent nerve biopsy. RESULTS: A diagnosis of leprosy was confirmed in 14 patients and was highly probable in 17 others. Eleven patients had vasculitic neuropathy, and in 1 patient there were amyloid deposits on nerve biopsy. CONCLUSIONS: In 43 of 68 Indian patients (63%) with MM, nerve biopsy identified a definite (26 patients) or probable (17 patients) etiology. Nerve biopsy is a valuable investigation in MM that frequently results in a diagnosis of leprosy in India. Muscle Nerve, 2016 Muscle Nerve 55: 23-27, 2017.