Monomelic Amyotrophy/Hirayama Disease: Surgical Outcome in a Large Cohort of Indian Patients.

BACKGROUND: Hirayama disease (HD) is a cervical compressive myelopathy. Anterior cervical discectomy and fusion (ACDF) is identified as the best surgical approach. We evaluated surgical outcomes and factors influencing ACDF in HD. METHODS: Between 2015 and 2019, 126 patients with HD underwent ACDF. Contrast magnetic resonance imaging of the cervical spine in full flexion was performed. Clinical examination and preoperative/postoperative assessment of hand function using Fugl-Meyer assessment, Jebsen-Taylor hand function test, and handheld dynamometry were performed at 3-monthly intervals for 1 year. Surgical outcomes were assessed as per the Odom criteria and Hirayama outcome questionnaire. RESULTS: Age at onset and duration of illness were 12-31 years (mean, 18 ± 2.7) and 1-96 months (32.7 ± 24.4), respectively. All patients had progressive weakness and wasting of the affected limb. Cord atrophy was seen in 97.1%, with epidural detachment and engorgement of the posterior epidural venous plexus in all. All patients underwent ACDF. Of these patients, 54% had an excellent/good outcome and 39% had a satisfactory outcome as per the Odom scale at last follow-up (mean, 44.9 ± 16.5 months) after surgery. Handheld dynamometry showed improvement from preoperative values to 1 year follow-up. Duration of illness and age at onset had a negative correlation and the preoperative Fugl-Meyer score had a positive correlation with improvement. CONCLUSIONS: ACDF resulted in remarkable improvement or stabilization in neurologic deficits in many patients with HD. Because motor disability ensues over time, early surgical intervention during the progressive phase is advocated.

Phenotype Genotype Characterization of FKRP-related Muscular Dystrophy among Indian Patients.

BACKGROUND: The phenotypic spectrum of Fukutin-related protein (FKRP) mutations is highly variable and comprises of limb girdle muscular dystrophy (LGMD) R9 (previously LGMD 2I) and FKRP related congenital muscular dystrophies. OBJECTIVE: To identify the distinct genotype phenotype pattern in Indian patients with FKRP gene mutations. METHODS: We retrospectively reviewed the case files of patients with muscular dystrophy having a genetically confirmed FKRP mutation. All patients had undergone genetic testing using next-generation sequencing. RESULTS: Our patients included five males and four females presenting between 1.5 years and seven years of age (median age - 3 years). The initial symptom was a delayed acquisition of gross motor developmental milestones in seven patients and recurrent falls and poor sucking in one patient each. Two patients had a language delay, with both having abnormalities on the brain MRI. Macroglossia, scapular winging, and facial weakness were noted in one, three and four patients respectively. Calf muscle hypertrophy was seen in eight patients and ankle contractures in six. At the last follow-up, three patients had lost ambulation (median age - 7 years; range 6.5-9 years) and three patients had not attained independent ambulation. Creatine kinase levels ranged between 2793 and 32,396 U/L (mean 12,120 U/L). A common mutation - c.1343C>T was noted in 5 patients in our cohort. Additionally, four novel mutations were identified. Overall, six patients had an LGMD R9 phenotype, and three had a congenital muscular dystrophy phenotype. CONCLUSION: Patients with FKRP mutations can have varied presentations. A Duchenne-like phenotype was the most commonly encountered pattern in our cohort, with c.1343C>T being the most common mutation.

Inflammatory myofibroblastic tumors: A short series with an emphasis on the diagnostic and therapeutic challenges.

BACKGROUND: Inflammatory myofibroblastic tumors (IMTs) are a distinct entity of mesenchymal tumors. We present the challenges in their diagnosis and management. MATERIALS AND METHODS: A retrospective study with detailed clinical, radiological, and histopathological (HPE) features along with management and outcome of 10 biopsy-proven patients with IMT, between 2001 and 2020. RESULTS: The location included intracranial (5), orbital (4), and spinal (1) with M : F = 7 : 3. The mean age of onset was in the third decade. The commonest symptom was headache, while proptosis and blurred vision occurred in orbital IMTs. HPE revealed diffuse infiltration of mixed inflammatory cells over proliferating myofibroblasts. Smooth muscle antigen immunoreactivity was noted in fibroblastic spindle cells of all IMTs. However, we did not find anaplastic lymphoma kinase expression in any of our cases, as this is only found in ~ 50% of all IMTs. Tumor infiltration into adjacent tissue was noted in 4 patients. Surgical excision was limited to orbital IMTs, as most central nervous system (CNS) tumors were not amenable for resection. Steroid administration showed moderate improvement in the IMT-CNS patients but also required additional immunomodulation. Four patients had a median long-term follow-up of 7 years. Two patients had recurrent lesions demonstrated by imaging after 2 years of initial presentation. CONCLUSION: IMTs are rare and ambiguous tumors of unknown etiology that can occur anywhere in the body. Clinical and radiological features may not be specific to determine the diagnosis, but it should be considered as a differential diagnosis. Extensive thorough workup with histopathology along with the help of immunohistochemistry is conducive to better clinical outcomes. Surgical biopsy with extensive and total resection of these tumors along with steroid and radiotherapy may enhance the survival outcomes.

Thymic Lesions in Myasthenia Gravis: A Clinicopathological Study from India.

BACKGROUND AND OBJECTIVES: Thymic pathology is common in Myasthenia Gravis(MG) and plays a crucial role in its pathogenesis and clinical outcome. This study aims to discuss the clinicohistopathological spectrum of thymic lesions in MG. METHODS: In this retrospective study, MG patients who underwent thymectomy from 2011 to 2020 were included. Clinical, radiological, serological, and histopathological details are described. RESULTS: Of 83 patients(F = 45; M = 38), 7(8%) had ocular myasthenia, and the remaining 76(92%) had the generalized form. At onset, the median age was 36 years(M = 44; F = 31). AChR antibody was positive in 71/79 patients. RNST showed decrement response in 68/78 patients. The histopathological study demonstrated thymoma in 44(53%), thymic hyperplasias [32(38%)], involuted thymus [5(6%)], thymic cyst (1) and thymic lipoma (1). WHO grading of thymoma: B2- 48%, AB-18%, B-18%, B3-14%, A-2.3%. In these, capsular infiltration was noted in 11/44, 9 had focal and 2 had diffuse infiltration. Active germinal centers were present in 20/32 patients with thymic hyperplasia and 4/44 with thymoma. Thymomas were predominant in males and thymic hyperplasia in females. The age of onset and antibody positivity rate was higher in thymoma patients. CONCLUSION: In our cohort, there is a female preponderance. Thymoma was the commonest pathology followed by hyperplasia. We observed earlier onset of myasthenia in females. AChR antibody positivity rate was more frequent in thymomas. This study indicates that clinico-radiological evaluation adequately supported by serology and histopathology can effectively recognize the type of thymic pathology that can guide these patients' treatment planning, management, prognosis and follow-up.

Clinical, genetic profile and disease progression of sarcoglycanopathies in a large cohort from India: high prevalence of SGCB c.544A > C.

The clinico-genetic architecture of sarcoglycanopathies in Indian patients is reported only as short series. In the present study, we aimed to investigate the clinical picture, genetic basis, and disease progression of patients genetically confirmed to have sarcoglycanopathy. Next-generation sequencing was performed in 68 probands with suspected sarcoglycanopathy. A total of 35 different variants were detected in the sarcoglycan genes in 68 probands (M = 37; age range, 5-50 years). Consanguinity was present in 44 families. Thirty-two variants are predicted to be pathogenic/likely pathogenic, among which 25 (78.13%) are reported, and 7 (21.87%) are novel. The clinical diagnosis was confirmed in a total of 64 (94.12%) probands with biallelic variations [SGCA(n=18); SGCB(n=34); SGCG(n=7); SGCD(n=5)]. The most common mutation was c.544A > C (p.Thr182Pro) in SGCB, and detected in 20 patients (29.42%). The majority of pathogenic mutations are homozygous (n = 30; 93.75%). Variants in 4 cases are of uncertain significance. Thirty-three patients lost ambulation at a mean age of 15.12 ± 9.47 years, after 7.76 ± 5.95 years into the illness. Only 2 patients had cardiac symptoms, and one had respiratory muscle involvement. The results from this study suggest that mutations in SGCB are most common, followed by SGCA, SGCG, and SGCD. The novel variations identified in this study expand the mutational spectrum of sarcoglycanopathies. To the best of our knowledge, this is the first study from India to describe a large cohort of genetically confirmed patients with sarcoglycanopathy and report its disease progression.