Sporadic Inclusion Body Myositis: A Clinicopathological Study.

BACKGROUND: Sporadic inclusion body myositis (s-IBM) is rare in India. AIM: The aim of this study was to diagnose s-IBM according to the European Neuromuscular Center (ENMC) IBM research diagnostic criteria 2011. MATERIALS AND METHODS: A retrospective review of patient records diagnosed as s-IBM according to the above criteria during the period from January 2010 to May 2015 was done with an emphasis on pattern of muscle weakness.Serumcreatine kinase (CK) andelectromyography (EMG) were noted. Muscle biopsy was evaluated with basic panel of histochemical stains including Congo red stain. Immunohistochemistry (IHC) with ubiquitin was done in 10 biopsies. IHC for major histocompatibility complex-1 and electron microscopy studies were not performed. RESULTS: The diagnosis of s-IBM constituted 5 clinicopathologically defined, 12 clinically defined, and 10 probable IBM in the study period. There was male predominance with median age at 51 and duration of disease varying from 1-5 years. All the patients presented with insidious onset of muscle weakness of quadriceps and/or forearm flexors. CK varied from 57-2939 IU/L. EMG was myopathic in 22, mixed in 2, and neuropathic in 3. Endomysial inflammation was seen in 23 (85.19%) and rimmed vacuoles in 24 (88.89%). Amyloid was demonstrated in only 5 (18.52%) and ubiquitin in 2 biopsies. Mitochondrial abnormalities were seen in 92.59% biopsies. CONCLUSIONS: Application of the ENMC IBM research diagnostic criteria allowed diagnosis of clinically-defined and probable IBM in the absence of all pathology criteria. Rimmed vacuoles in 88.89% of biopsies indicate presentation at a late stage. Use of ancillary techniques can improve diagnostic yield.

Functional Outcome of Bilateral Subthalamic Nucleus-Deep Brain Stimulation in Advanced Parkinson's Disease Patients: A Prospective Study.

BACKGROUND: Deep brain stimulation (DBS) is an accepted modality of treatment in patients with Parkinson's disease (PD). Although DBS was approved in advanced PD, it is being done in early PD as well. It was mainly developed to help the patients of PD to overcome the adverse motor effects associated with treatment and treatment failure. OBJECTIVE: The objective is to study the efficacy of subthalamic nucleus (STN)-DBS procedure in patients with PD. MATERIALS AND METHODS: This was a prospective, single-center, follow-up observational study using a direct, structured interview of 40 selected PD patients. Preoperative assessment using Unified PD Rating Scale-III (UPDRS-III), Montreal Cognitive Assessment (MOCA), and Parkinson's Disease Questionnaire-39 were done. All the patients underwent DBS. Postoperatively, similar assessment was done during follow-up period of 6 months. The results were analyzed using Student's t-test. RESULTS: The total score of UPDRS-III was reduced by 35% after STN-DBS intervention which was statistically significant (P < 0.05). STN-DBS intervention was successful in significantly reducing all UPDRS-III subscores but failed to reduce the scores in case of postural stability. MOCA scores of the patients were not found to be affected by STN-DBS intervention (P = 0.1466). Similar findings were also observed for MOCA subscores, but there was significant improvement of verbal fluency in all patients. Quality of life(QoL) improved significantly in all patients after STN-DBS intervention in all areas. Lower baseline UPDRS-III scores were found to enhance the QoL both in "off" and "on" state. However, prolonged disease duration and older age at PD onset were found to be hampering factors in the improvement of QoL. CONCLUSIONS: STN-DBS is a safe procedure and can be performed in all patients of PD who develop disabling motor fluctuations to improve their QoL irrespective early or advanced disease.

C4d as a marker of complement activation in dermatomyositis muscle tissue.

AIM: To study C4d expression as a marker of complement activation in the diagnosis of dermatomyositis. MATERIAL AND METHODS: Muscle biopsies from patients diagnosed as definite dermatomyositis (10), nonspecific myositis associated with connective tissue disease (9), necrotizing autoimmune myositis (1), inclusion body myositis (1), and normal muscle (1) according to European Neuromuscular criteria 2004 were studied for C4d expression and capillary loss on CD 34 immunohistochemistry. RESULTS: C4d was expressed in all biopsies of definite dermatomyositis in the perimysial vessels and in 3/10 endomysial capillaries corresponding to capillary loss on CD 34.C4d expression was seen in 2/3 perimysial and endomysial vessels in nonspecific myositis (2/3 overlap myositis), and 1/1 of nectrotizing autoimmune myositis.Necrotic muscle fibers in all biopsies showed positivity irrespective of the diagnosis. CONCLUSION: C4d can be used as a marker of complement activation for the diagnosis of dermatomyositis.

Idiopathic inflammatory myopathies in adults: A comparative study of Bohan and Peter and European Neuromuscular Center 2004 criteria.

BACKGROUND: Bohan and Peter criteria are widely used for the diagnosis of idiopathic inflammatory myopathies (IIMs). Recently, European Neuromuscular Center (ENMC) formulated criteria to identify subgroups of IIMs. AIM: To compare the two diagnostic criteria in adult IIMs. MATERIALS AND METHODS: This was a retrospective review of case records of histologically confirmed IIMs in adults between January 2014 and May 2015. Both the Bohan and Peter, and ENMC 2004 criteria were applied in the same group of patients to subgroup the IIMs. Muscle biopsy was evaluated in all the four domains: muscle fiber, inflammatory, connective tissue, and vascular, with the basic panel of histological stains. Sporadic inclusion body myositis (s-IBM) was diagnosed using ENMC IBM diagnostic research criteria 2011. RESULTS: During the study period, 69 patients fulfilled the ENMC criteria for IIMs including 16 patients with s-IBM. The subgrouping as per the ENMC criteria (53) was: dermatomyositis (DM) in 30; polymyositis (PM) in 2; immune-mediated necrotizing myopathy (IMNM) in 9; and nonspecific myositis (NM) in 12 patients, whereas subgrouping by the Bohan and Peter criteria was DM in 9 and PM with and without connective tissue disease (CTD) in 26 patients only. There was underdiagnosis of DM, as perifascicular atrophy is not recognized as a diagnostic histological feature, and overdiagnosis of PM with and without CTD due to poor characterization of histological features in PM by the Bohan and Peter criteria. CONCLUSIONS: Systematic evaluation of muscle biopsy according to the ENMC criteria with basic panel of histochemical stains improved the diagnostic yield of IIM significantly when compared to the Bohan and Peter criteria.

Series of paraneoplastic vasculitic neuropathy: a rare, potentially treatable neuropathy.

BACKGROUND: Paraneoplastic vasculitic neuropathy (PVN) is a rare paraneoplastic syndrome. It is characterized by non-systemic subacute vasculitic neuropathy. It is most commonly associated with small cell lung cancers (SCLC) and lymphomas. PVN presents as a painful symmetrical or asymmetrical sensorimotor axonal neuropathy. The neurological symptoms may predate the tumor and may be the initial manifestations, or they may develop after a tumor is diagnosed. Recognition of this entity is important because of its potential treatability. AIM: To study the clinical features of PVN and briefly review the literature. MATERIALS AND METHODS: The data was collected retrospectively from the medical records of our hospital. RESULTS: Of the 14 cases of paraneoplastic neuropathies, 4 had a PVN. The age of onset was more than 50 years and there was no sex preponderance. Pain was seen in three patients. Two patients were previously treated for a thymoma. Two patients, following their presentation with PVN, were diagnosed with a colonic carcinoma and lung carcinoma, respectively. CONCLUSIONS: The recognition of PVN is important as this syndrome may respond to immunosuppression and tumor removal.

Prevalence of neuropathy in patients with impaired glucose tolerance using various electrophysiological tests.

BACKGROUND: Neuropathy is often an associated feature woth long-standing type II diabetes mellitus. Neuropathy may occur even in subjects with impaired glucose tolerance. OBJECTIVE: To study the prevalence of neuropathy using different electrophysiological techniques in subjects with impaired glucose tolerance (IGT) and no other identifiable cause of neuropathy. MATERIALS AND METHODS: The study was conducted on 30 age-matched controls and 58 subjects with impaired oral glucose tolerance test (OGTT) attending diabetic awareness. Prediabetes was defined using World Health Organization (WHO) criteria. All subjects had normal glycosylated hemoglobin HbA (1c), vitamin B12 levels, and thyroid function. Neuropathy was evaluated by nerve conduction studies (NCS) performed on one upper and both lower limbs, dorsal sural nerve, medial and lateral planter nerve conductions using conventional techniques. Neuropathy was also evaluated by autononic function tests, and quantitative sensory testing (QST). The subjects were followed up for 4 years. RESULTS: Out of 58 subjects, 19 (32.8%) had neuropathy. Nerve conduction studies showed evidence of neuropathy in 14 (24.13%) subjects, autonomic neuropathy was detected in 8 (13.8%), and QST was found to be abnormal in 16 (27.6%) subjects. Twenty subjects (34.5%) developed diabetes mellitus in the follow-up period. CONCLUSIONS: Neuropathy was detected in 32.8% subjects with IGT. Small fiber neuropathy was most common. Of all the three parameters studied, QST was found to be most sensitive technique for the detection of neuropathy. Assessment of medial plantar and dorsal sural NCS increases the sensitivity in the detection of neuropathy.

Incidence of malignancies in biopsy-proven inflammatory myopathy.

BACKGROUND: Inflammatory myopathy (IM) as a manifestation of paraneoplastic syndrome has been well-documented. However, the prevalence of malignancies reported varies across the studies. There are very few studies reported from Asia, only one from India. AIM: The aim of this analysis was to study the prevalence of malignancy in biopsy-proven cases of IM in India and to study the difference between malignant and non-malignant groups. MATERIALS AND METHODS: The study was a retrospective review of case records of patients with a biopsy-proven IM attending Tertiary Care University Hospital. RESULTS: Of the total 86 patients with biopsy-proven IM, 22 patients were polymyositis, 63 patients had dermatomyositis (DM) and one was with an inclusion body myositis, not included for further analysis. Associated malignancy was diagnosed in 6 (7%) patients, and five of them were females. Diagnosis of associated malignancy was identified at the time of diagnosis of IM in four (66.7%) patients. All the six patients with an associated malignancy had DM. Only one patient died within 1 year of diagnosis. Creatinine kinase was much lower in patients with malignancy associated IM than in patients with no malignancy (P < 0.0001). CONCLUSION: The prevalence of malignancy was very low in our cohort as compared to the studies from other countries. Breast cancer was the most common malignancy associated with DM. The type of associated malignancy was quite variable.

Distal myopathy with rimmed vacuoles and inflammation: a genetically proven case.

Distal myopathy with rimmed vacuoles (DMRV) is a major entity of distal myopathy. It is an autosomal recessive disorder and is due to mutations in the GNE gene that regulates the synthesis of sialic acid. Although reported predominantly from Japan, cases have been reported from other parts of the world. We report the first genetically proven case of DMRV from India in a 23-year-old male with gradual onset, progressive distal weakness of both lower limbs with features of inflammation in muscle biopsy.

Clinical, electrophysiological subtypes and antiganglioside antibodies in childhood Guillain-Barré syndrome.

BACKGROUND: Guillain-Barré syndrome (GBS) has been the most common cause of flaccid paralysis in children after the decline in the incidence of poliomyelitis. There are not any published data from the Indian subcontinent documenting electrophysiological patterns and antiganglioside antibodies in pediatric GBS. MATERIALS AND METHODS: The study population included children with GBS referred for electrodiagnostic evaluation and also children with GBS admitted to our institute between August 2006 and July 2007. Nerve conduction studies were done to determine GBS subtypes and serum antiganglioside antibodies were measured using enzyme-linked immunosorbent assay (ELISA). Clinical and electrophysiological features were correlated with antiganglioside antibody results. RESULTS: Of the 43 (male to female ratio = 2.1:1) children studied, 97.6% had motor weakness, 76.7% had cranial nerve palsies, 13.9% had autonomic disturbances and respiratory paralysis was found in 9.3% children. Antecedent illness was recorded in 69.8% children. The GBS subtype distribution was as follows: acute inflammatory demyelinating polyradiculoneuropathy (AIDP) in 21 (48.8%), acute motor axonal neuropathy (AMAN) in 19 (44.2%), and 3 (6.9%) children were unclassified. The severity of illness was similar in both AMAN and AIDP subtypes and the recovery in both the subtypes was complete without any significant difference in the duration of recovery. Preceding diarrheal illness was more common in AMAN subtype as compared to AIDP subtype (57.9% vs. 4.7%, P = 0.007). Sensory symptoms were more common in AIDP subtype than in AMAN subtype (66.6% vs. 21%, P = 0.03}. The commonest ganglioside antibody was IgM GM2. Anti GM3 antibodies were exclusively seen in children with AMAN and IgG GD1b was significantly associated with (36.7 vs. 4%; P = 0.007) AMAN subtype. IgG GT1b was identified in 50% of patients with AIDP as compared to 22.7% in patients with AMAN. CONCLUSION: In this study, AMAN subtype accounted for a significant proportion of pediatric GBS. AMAN was associated with diarrhea and specific antiganglioside antibodies. Recovery in children with GBS was complete, irrespective of the subtype.