A.K. Meena

Second lumbrical and interossei latency difference in Carpal Tunnel Syndrome

OBJECTIVE To evaluate the diagnostic value of second lumbrical and interossei distal motor latency difference (2LIDMLD) in diagnosing CTS of different electro-physiological grades of CTS. METHODS 2LIDMLD was standardized in 120 hands of healthy controls. Subjects with clinically diagnosed CTS and CTS with incidental polyneuropathy were prospectively evaluated with 2LIDMLD in addition to other standard diagnostic tests. Sensitivities of these tests were compared in patients with CTS of varying grades of severity and CTS associated with polyneuropathy. RESULTS Two hundred and fifty hands of 130 patients met the clinical criteria for CTS. Sensitivity and specificity of 2LIDMLD, palm-wrist distal sensory latency difference (PWDSLD), and median distal motor latency (MDML) were 85.60% and 96.67%, 68.80% and 96.10%, 60.80% and 97%, respectively. Sensitivity of 2LIDMLD in mild CTS was similar to that of PWDSLD. In severe CTS, and CTS with polyneuropathy, 2LIDMLD was the most sensitive test. It was the only test of localizing value in 16% of hands with severe CTS, when all other methods failed due to absent median motor and sensory responses. CONCLUSIONS 2LIDMLD is a sensitive, specific for diagnosis of all grades of CTS. It is an accurate and reliable method that helps especially in diagnosis of severe CTS and CTS associated with polyneuropathy, when other standard localized tests fail. SIGNIFICANCE The second lumbrical is relatively less affected in severe carpal tunnel syndrome and median to ulnar comparison, using 2LIDMLD, appears to be a reliable and a valuable technique in the localization of severe CTS and CTS associated with polyneuropathy, especially when the median sensory or motor responses are absent on routine conduction studies.

Mitochondrial disorders: Challenges in diagnosis & treatment

Mitochondrial dysfunctions are known to be responsible for a number of heterogenous clinical presentations with multi-systemic involvement. Impaired oxidative phosphorylation leading to a decrease in cellular energy (ATP) production is the most important cause underlying these disorders. Despite significant progress made in the field of mitochondrial medicine during the last two decades, the molecular mechanisms underlying these disorders are not fully understood. Since the identification of first mitochondrial DNA (mtDNA) mutation in 1988, there has been an exponential rise in the identification of mtDNA and nuclear DNA mutations that are responsible for mitochondrial dysfunction and disease. Genetic complexity together with ever widening clinical spectrum associated with mitochondrial dysfunction poses a major challenge in diagnosis and treatment. Effective therapy has remained elusive till date and is mostly efficient in relieving symptoms. In this review, we discuss the important clinical and genetic features of mitochondrials disorders with special emphasis on diagnosis and treatment.

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 mutation in C10orf2 associated with multiple mtDNA deletions, chronic progressive external ophthalmoplegia and premature aging.

Chronic progressive external ophthalmoplegia (CPEO) is caused by defects in both mitochondrial and nuclear genes, however, the causal genetic factors in large number of patients remains undetermined. Therefore, our aim was to screen 12 unrelated patients with CPEO for mutation/multiple deletions in mtDNA and mutations in the coding regions of C10orf2, which is essential for mtDNA replication. Histopathological study of muscle biopsy revealed cytochrome c oxidase-deficient fibers and ragged blue fibers in all the patients. Long-range PCR of DNA from skeletal muscle revealed multiple mtDNA deletions in all the 12 patients. Further, sequencing coding regions of C10orf2 revealed three variants in three different patients, of which two were novel (c.1964G>A/p.G655D; c.204G>A/p.G68G) variants and one was reported (c.1052A>G/p. N351S). Sequencing of other nuclear genes that are associated with CPEO and multiple mtDNA deletions, such as; POLG1, POLG2, TK2, ANT1, DGUOK, MPV17 and RRM2B did not reveal any pathogenic mutation in patients with C10orf2 mutation. Since in silico analyses revealed p.G655D could be a potentially pathogenic and it was absent in 200 healthy controls, p.G655D could be the causative factor for CPEO. Therefore, we suggest that C10orf2 gene should be screened in CPEO individuals with multiple mtDNA deletions, which might help in prognosis of this disease and appropriate genetic counseling.

MPV17 hepatocerebral mitochondrial DNA depletion syndrome presenting as acute flaccid paralysis – A case report

Mutations in human MPV17 have been reported in patients with severe mitochondrial DNA (mtDNA) depletion manifesting as early childhood onset failure to thrive, hypoglycemia, encephalopathy and progressive liver failure. We describe an 11 year old girl, born to consanguineous parents, who presented with rapidly progressive weakness of all 4 limbs with symmetrical proximal and distal weakness, gastrointestinal disease and leukoencephalopathy. Genetic analysis of the patient revealed a homozygous pathogenic mutation c.121C>T (p.R41W) in the MPV17 gene. Further, screening for this mutation in the parents revealed the presence of heterozygous mutation in both the parents, suggesting the recessive nature of the disease.

P34-21 Utility of various tests in diagnosis of ocular myasthenia gravis

Background and Objective: In typical cases, the patient’s history and clinical examination help to diagnose ocular myasthenia gravis (OMG). But, in many cases this is not so. MG lacks a diagnostic gold standard, so diagnosis is supported by several tests. Diagnostic tests for OMG are usually unable to display a good sensitivity and specificity simultaneously. This study aims to study various tests in these patients and compare their significance in the diagnosis of OMG. Material and Methods: Study included consecutive patients over 1 year with clinically suspected OMG. Clinical, electrophysiological and other tests were performed to diagnose OMG. (Neostigmine test, Icepack test, Repetitive nerve stimulation (RNS), Single fiber electromyography (SFEMG), Anti-AChR antibody titers and CT chest for thymoma). RNS was done in Abductor digiti quinti, Nasalis, and Trapizeus muscles.SFEMG was performed in frontalis and Extensor digitorum communis (EDC) recording 20 potential pairs. SFEMG was considered positive when jitter, expressed as mean consecutive difference (MCD), was increased in 15% or more potential pairs or in the case of an abnormal mean MCD associated with at least 2/20 abnormal potential pairs. Results: Amongst thirty patients male to female sex ratio was 18:12. Mean age range was 35.45±20.31 years. RNS was positive in 1 patient (1/30). Neostigmine test was negative in 4 patients (4/26; 15.38%); with sensitivity, specificity and positive predictive value of 86.67% and 80%, 92.85% respectively. Icepack test was negative in 3 patients (3/26; 11.5%) and sensitivity, specificity 90%, 100% respectively. Positive predictive value was 100%. SFEMG was positive in 29 patients (29/30; 96.66%; sensitivity 96.66%, specificity 90%, positive predictive value-96.66%). In 3 patients SFEMG in EDC was negative. AchR Ab was positive in 40% (8/20). Thymoma was seen in 1 patient (1/12). Conclusion: Among various tests, the most sensitive and specific nonivasive and invasive diagnostic tests for OMG is Icepack test and SFEMG.

PF3.2 Prevalence of Neuropathy in Prediabetic Subjects Using Various Electrophysiological Techniques

Background: Guillain Barré syndrome (GBS) is an acute immunedmediated polyneuropathy often after an antecedent infection. There are at least four subtypes based on clinical and electrophysiological findings: acute inflammatory demyelinating polyneuropathy (AIDP), acute motor and sensory axonal neuropathy (AMSAN), acute motor axonal neuropathy (AMAN) and Miller-Fisher syndrome (MFS). We describe the spectrum of GBS seen in a Malaysian population. Methods: GBS patients seen between 1995 and 2008 at the University of Malaya Medical Centre, Kuala Lumpur were included. The UMMC is a tertiary neurological referral centre for the country. Demographic data, clinical presentation and electrophysiological findings were reported. Diagnosis of GBS and its classification was based on clinical findings and the electrophysiological criteria of Hadden et al (1998). Results: There were 86 patients, 55 (64%) males. Mean age was 37.6 years (2 81). Ethnic backgrounds were Chinese 37 (43%), Malay 24 (27.9%), Indian 22 (25.6%) and other races 3 (3.5 %). Based on the initial electrophysiological study, 50 (58.1%) were AIDP and 11 (12.8%) had axonal neuropathy. Of these, 7 were AMAN and 4 were AMSAN. A further 15 (17.4%) had indeterminate electrophysiological findings, one (1.2%) had inexcitable nerves and six (7%) normal findings. Ten (11.6%) patients had MFS, which 4 had indeterminate electrophysiological findings and six normal findings. The majority of our patients, 72 (83.7%) were from urban areas. Conclusions: Unlike the spectrum of GBS seen in other developing countries such as northern China and Mexico, the spectrum in a mainly urban Malaysian population suggests a predominance of AIDP rather than axonal forms of GBS. There is also a relatively high percentage of MFS in our population.