Haplogroup heterogeneity of LHON patients carrying the m.14484T>C mutation in India

Purpose: To investigate the clinical and mitochondrial DNA (mtDNA) haplogroup background of Indian Leber Hereditary Optic Neuropathy (LHON) patients carrying the m.14484T>C mutation. Methods: Detailed clinical investigation and complete mtDNA sequencing analysis was carried out for eight Indian LHON families with the m.14484T>C mutation. Haplogroup was constructed based on the evolutionarily important mtDNA variants. Results: In the present study, we characterized eight unrelated probands selected from 187 LHON cases. The overall penetrance of the disease was estimated to be 19.75% (16/81) in eight pedigrees with the m.14484T>C mutation and showed substantially higher sex bias (male:female = 13:3). The mtDNA haplogrouping revealed that they belong to diverse haplogroups; i.e. F1c1, M31a, U2a, M*, I1, M6, M3a1 and R30a. Interestingly, we did not find an association of the m.14484T>C mutation with any specific haplogroup within the Indian population. We also did not find any secondary mutation(s) in these pedigrees, which might affect the clinical expression of LHON. Conclusions: Contrary to earlier reports showing preferential association of the m.14484T>C mutation with western Eurasian haplogroup J and increased clinical penetrance when present in J1 subhaplogroup background, the present study shows that m.14484T>C arose independently in a different mtDNA haplogroup and ethnic background in India, which may influence the clinical expression of the disease

Novel SPG11 mutations in Asian kindreds and disruption of spatacsin function in the zebrafish

Autosomal recessive hereditary spastic paraplegia with thin corpus callosum (HSP-TCC) maps to the SPG11 locus in the majority of cases. Mutations in the KIAA1840 gene, encoding spatacsin, have been shown to underlie SPG11-linked HSP-TCC. The aim of this study was to perform candidate gene analysis in HSP-TCC subjects from Asian families and to characterize disruption of spatacsin function during zebrafish development. Homozygosity mapping and direct sequencing were used to assess the ACCPN, SPG11, and SPG21 loci in four inbred kindreds originating from the Indian subcontinent. Four novel homozygous SPG11 mutations (c.442+1G>A, c.2146C>T, c.3602_3603delAT, and c.4846C>T) were identified, predicting a loss of spatacsin function in each case. To investigate the role of spatacsin during development, we additionally ascertained the complete zebrafish spg11 ortholog by reverse transcriptase PCR and 5′ RACE. Analysis of transcript expression through whole-mount in situ hybridization demonstrated ubiquitous distribution, with highest levels detected in the brain. Morpholino antisense oligonucleotide injection was used to knock down spatacsin function in zebrafish embryos. Examination of spg11 morphant embryos revealed a range of developmental defects and CNS abnormalities, and analysis of axon pathway formation demonstrated an overall perturbation of neuronal differentiation. These data confirm loss of spatacsin as the cause of SPG11-linked HSP-TCC in Asian kindreds, expanding the mutation spectrum recognized in this disorder. This study represents the first investigation in zebrafish addressing the function of a causative gene in autosomal recessive HSP and identifies a critical role for spatacsin during early neural development in vivo

Urodynamic profile of patients with neurogenic bladder following non-traumatic myelopathies

Objective: To observe the urodynamic profile of the patients following non-traumatic myelopathies (NTMs) with neurogenic bladder. Setting: Neurological rehabilitation department of university tertiary research hospital. Materials and Methods: Seventy-nine patients (44 men) with monophasic NTM, with the age range 8-65 years (31.0 ± 16.0 years), were admitted for inpatients′ rehabilitation. Length of stay in rehabilitation ranged from 6 to 120 days (32.0 ± 24.8 days). Fifty-six patients (70.9%) had spinal lesion above D10, 17 had lesion between D10 and L2 (21.5%), and 6 (7.6%) had cauda equina syndrome. All patients had neurogenic bladder with urinary complaints. Urodynamic study (UDS) was performed in all patients. Results: UDS showed 71.4% patients (40/56) had neurogenic detrusor overactivity (NDO) with or without sphincter dyssynergy (DSD) with lesion above D10; only 52.9% patients (9/17) had NDO with or without DSD detrusor with lesion between D10 and L2; and majority (5/6 patients) had underactive detrusor in the cauda equina group. Bladder management was based on the UDS findings. No significant correlation was found (P > 0.05) between detrusor behavior and the level, severity (ASIA Impairment Scale) of spinal injury, or gender using chi-square test. Conclusions: Neurogenic bladder following NTM was observed in all patients. UDS suggested predominantly NDO in lesions above D10 and mixed pattern in between D10 and L2 lesions. No significant correlation was found between detrusor behavior and the level or severity of NTM in the study

Urodynamic profile in acute transverse myelitis patients: Its correlation with neurological outcome

Objective: The objective of this study was to observe urodynamic profile of acute transverse myelitis (ATM) patients and its correlation with neurological outcome. Patients and Methods: This prospective study was conducted in the neurorehabilitation unit of a tertiary university research hospital from July 2012 to June 2014. Forty-three patients (19 men) with ATM with bladder dysfunction, admitted in the rehabilitation unit, were included in this study. Urodynamic study (UDS) was performed in all the patients. Their neurological status was assessed using ASIA impairment scale and functional status was assessed using spinal cord independence measure. Bladder management was based on UDS findings. Results: In total, 17 patients had tetraplegia and 26 had paraplegia. Thirty-six patients (83.7%) had complaints of increased frequency and urgency of urine with 26 patients reported at least one episode of urge incontinence. Seven patients reported obstructive urinary complaints in the form of straining to void with 13 patients reported both urgency and straining to void and 3 also had stress incontinence. Thirty-seven (86.1%) patients had neurogenic overactive detrusor with or without sphincter dyssynergia and five patients had acontractile detrusor on UDS. No definitive pattern was observed between neurological status and bladder characteristics. All patients showed significant neurological and functional recovery with inpatient rehabilitation (P< 0.05 and P< 0.001, respectively). Conclusions: The problem of neurogenic bladder dysfunction is integral to ATM. Bladder management in these patients should be based on UDS findings. Bladder characteristics have no definitive pattern consistent with the neurological status

Vasculitic neuropathy in elderly: A study from a tertiary care university hospital in South India

Objective: To describe clinical, electrophysiological, and histopathological profile of vasculitic neuropathy in elderly subjects aged 65 years or more. Design: Retrospective chart review. Setting: Departments of Neurology and Neuropathology, National Institute of Mental Health and Neurosciences, Bengaluru, Karnataka, India. Patients and Methods: Elderly subjects, diagnosed vasculitic neuropathy by nerve biopsy over one decade, were studied. Results: The cohort consisted of 46 subjects. Symptom duration was 21.54 ± 33.53 months. Onset was chronic in majority (82.6%). Key features included paresthesias (89%), weakness (80%), sensory loss (70%), wasting (63%), and relapsing-remitting course (6.5%). Most Common clinico-electrophysiological patterns were distal symmetrical sensorimotor polyneuropathy - 19, mononeuritis multiplex - 9, and asymmetric sensorimotor neuropathy - 10. Diagnosis of vasculitis was not suspected before biopsy in 31 (67.3%). Nerve biopsy revealed definite vasculitis - 12, probable - 10, and possible - 24. Treatment included immunomodulatory agents (41), symptomatic medications only (9), and antiretroviral therapy (1). Twenty-four patients were followed up for mean period of 6.5 months. Outcome at last follow-up was improved (13), unchanged (8), and worsened (3). Conclusion: Vasculitis is an important, treatable cause of neuropathy in elderly. Nerve biopsy should be used judiciously for early diagnosis and appropriate treatment

Urodynamics post stroke in patients with urinary incontinence: Is there correlation between bladder type and site of lesion?

<b>Objective:</b> Assessment of bladder by urodynamic study (UDS) in patients with urinary incontinence following stroke, and correlation with site of lesion.<b> Study Design and Setting:</b> Retrospective cross-sectional study in the neurological rehabilitation unit of a tertiary care institute.<b> Materials and Methods:</b> Forty patients (22 males) with arterial or venous, ischemic or hemorrhagic stroke, with urinary incontinence in the acute phase following the event, underwent UDS. Seventeen patients had right hemiplegia, 18 had left hemiplegia, and five had posterior circulation stroke with brainstem/cerebellar features. Bladder type was correlated with age, side, and site of lesion.<b> Results: </b> The mean age was 46.80 &#x00B1; 16.65 years (range: 18-80 years). Thirty-six patients had arterial stroke and four had cortical venous thrombosis. UDS was performed after a mean of 28.32 &#x00B1; 10.27 days (range: 8-53 days) after the stroke. All but one patient had neurogenic bladder dysfunction, with 36 patients (90&#x0025;) having overactive detrusor (OD) and three having underactive/areflexic detrusor. Among the 36 patients with OD, 25 patients (62.5&#x0025;) had OD without detrusor-sphincter dyssynergy (DSD) and 11 (27.5&#x0025;) had OD with DSD. Bladder management was advised based on the UDS findings. No significant correlation (<i> P </i> &gt; 0.05) was found between type of bladder and age or side and site of lesion. <b> Conclusions: </b> UDS is a useful tool to assess and manage the bladder following stroke with urinary incontinence. In this study, no significant correlation was found between UDS findings and site of lesion

Sexual Dysfunction and Sexual Concerns among Persons with Disability Due to Myelopathy: A Cross-Sectional Study

Background We have very little information about sexual activity and concerns of patients with myelopathy from India. Objectives This article assesses the sexual dysfunction and sexual concerns among patients with myelopathy due to spinal cord lesion (SCL). Materials and Methods Single-center, cross-sectional, hospital-based study among male and female patients in the age group of 18 to 50 years, with disability due to myelopathy due to SCL. The data were collected using a self-designed, pretested, semistructured questionnaire by face-to-face interview. Results Eighty participants were recruited in the study, of which 62 (77.5%) were men. The mean (standard deviation [SD]) age of the participants was 33.7 (8.6) years, and mean (SD) age at time of illness was 31.4 (8.6) years with median duration of 17 months. Among 62 males, psychogenic erection was impaired in 77.2%, reflex erection was impaired in 78.9%, and ejaculation was affected in 70.7%. Orgasm was absent or reduced in 66.1% males. Among 18 female participants, psychogenic genital arousal was reduced in 66.5%, reflex genital arousal was impaired in 55.5%, and orgasm was absent in 38.8% subjects. Sexual desire in these patients was unchanged in 41 (51.2%), and decreased or absent in 39 (48.8%). Sexual activity involvement was there in 46 (57.5%) and 34 (42.5%) had not involved in any kind of sexual activity after injury/illness. The main reasons of noninvolvement in sexual activity were bladder and bowel accidents, spasticity, and difficulty in positioning. Conclusion Comprehensive neurological rehabilitation should address sexual function of affected individual to allow them highest level of function and quality of life