Long-term efficacy and safety of safinamide as add-on therapy in early Parkinson's disease.

BACKGROUND AND PURPOSE: Safinamide is an α-aminoamide with both dopaminergic and non-dopaminergic mechanisms of action in Phase III clinical development as a once-daily add-on to dopamine agonist (DA) therapy for early Parkinson's disease (PD). METHODS: Study 017 was a 12-month, randomized, double-blind, placebo-controlled pre-planned extension study to the previously reported Study 015. Patients received safinamide 100 or 200 mg/day or placebo added to a single DA in early PD. The primary efficacy endpoint was the time from baseline (Study 015 randomization) to 'intervention', defined as increase in DA dose; addition of another DA, levodopa or other PD treatment; or discontinuation due to lack of efficacy. Safinamide groups were pooled for the primary efficacy endpoint analysis; post hoc analyses were performed on each separate dose group. RESULTS: Of the 269 patients randomized in Study 015, 227 (84%) enrolled in Study 017 and 187/227 (82%) patients completed the extension study. Median time to intervention was 559 and 466 days in the pooled safinamide and placebo groups, respectively (log-rank test; P = 0.3342). In post hoc analyses, patients receiving safinamide 100 mg/day experienced a significantly lower rate of intervention compared with placebo (25% vs. 51%, respectively) and a delay in median time to intervention of 9 days (P < 0.05; 240- to 540-day analysis). CONCLUSIONS: The pooled data from the safinamide groups failed to reach statistical significance for the primary endpoint of median time from baseline to additional drug intervention. Post hoc analyses indicate that safinamide 100 mg/day may be effective as add-on treatment to DA in PD.

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.

Corticobasal syndrome due to a thalamic tuberculoma and focal cortical atrophy.

Corticobasal syndrome (CBS) is characterised by asymmetric apraxia, cortical sensory loss, extrapyramidal features and cognitive decline. Although CBS is classically described as a taupathy, heterogeneity of its aetiology is increasingly recognised. Clinical presentation of CBS appears to reflect areas of the brain involved and not necessarily the nature of the underlying pathology. We report a patient in whom resolution of a thalamic tuberculoma was associated with progressive atrophy of the parietotemporal cortex, resulting in an unusual presentation of CBS.

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.

Chlamydia pneumoniae antibodies in various subtypes of ischemic stroke in Indian patients.

BACKGROUND: As infections occur more frequently in developing countries, we carried out this prospective case-control study, to establish the association, if any, between C. pneumoniae antibodies and ischemic stroke particularly in relation to its subtypes. DESIGN: Antibodies (IgG and IgA) to C. pneumoniae in serum were measured by microimmunofluorescence test in 200 consecutive ischemic stroke patients and 200 age and sex matched controls. RESULTS: Seventy two out of 200 ischemic stroke patients (36%) had positive C. pneumoniae antibodies (IgG or IgA), compared to 35 out of 200 controls (17.5%) (p<0.0001). IgG antibody was positive in 64/200 (32%) ischemic stroke patients, compared to 34/200(17%) controls (p<0.0001) and IgA was positive in 20/200(10%) ischemic stroke patients compared to 1/200(0.5%) controls (p<0.0001). Logistic regression analysis showed statistically significant association between C. pneumoniae antibody positivity and ischemic stroke, thereby establishing it as an independent risk factor. Prevalence of C. pneumoniae antibodies was significantly higher in all stroke subtypes (except the stroke of undetermined etiology) compared to controls. CONCLUSION: Significant and independent association was found between C. pneumoniae antibodies and ischemic stroke in this sample of south Indian population. The association was found in all ischemic stroke subtypes, except stroke of undetermined etiology.

Lamotrigine extended-release as adjunctive therapy for partial seizures.

OBJECTIVE: To evaluate the efficacy and tolerability of once-daily adjunctive lamotrigine extended-release (XR) for partial seizures in epilepsy. METHODS: Patients more than 12 years old diagnosed with epilepsy with partial seizures and taking one to two baseline antiepileptic drugs were randomized to adjunctive once-daily lamotrigine XR or placebo in a double-blind, parallel-group trial. The study comprised a baseline phase, a 7-week double-blind escalation phase, and a 12-week double-blind maintenance phase during which doses of study medication and concomitant antiepileptic drugs were maintained. RESULTS: Of the 243 randomized patients, 239 (118 lamotrigine XR, 121 placebo) entered the escalation phase and received study medication. Lamotrigine XR was more effective than placebo with respect to median percent reduction from baseline in weekly partial seizure frequency (primary endpoint-entire 19-week treatment phase: 46.6% vs 24.5%, p = 0.0001 [corrected] via Wilcoxon test; escalation phase: 29.8% vs 15.6%, p = 0.027; maintenance phase: 58.4% vs 26.8%, p [corrected] < 0.0001). The percentage of patients with >or=50% reduction in partial seizure frequency (44.0% vs 20.8%, p = 0.0002) [corrected] and time to >or=50% reduction in partial seizure frequency (p = 0.0001) [corrected] also favored lamotrigine XR over placebo. A similar pattern of results was observed for secondarily generalized seizures. The most common adverse events were headache (lamotrigine XR 16%, placebo 18%) [corrected] and dizziness (lamotrigine XR 19%, [corrected] placebo 5%). Differences between lamotrigine XR and placebo on health outcomes measures were not significant. CONCLUSIONS: Once-daily adjunctive lamotrigine extended-release compared with placebo effectively reduced partial seizure frequency and was well tolerated in this double-blind study. Results support the clinical utility of this new once-daily formulation.

Sarcoglycanopathies: a clinico-pathological study.

BACKGROUND: Limb girdle muscular dystrophy (LGMD) is a heterogeneous group of disorders characterized by limb girdle weakness. There are no clear clinical features that distinguish various types of LGMD. MATERIALS AND METHODS: We studied 26 patients with chronic progressive weakness in limb girdle distribution without early facial involvement with muscle biopsies suggestive of dystrophy/myopathy and positive for dystrophin antibodies. Immunohistochemistry studies of muscle biopsies were done on all patients to classify different types of sarcoglycanopathies. RESULTS: The mean age of presentation was in the third decade. There were 14 male and 12 female patients. The common pattern of inheritance was autosomal recessive, seen in 53.8%. The more frequent type of LGMD was sarcoglycanopathy (SGP) (53.8%). Amongst the SGPs, alpha-SGP (26.9%) was the most common followed by beta-SGP (15.3%), gamma-SGP (3.8%) and delta-SGP (7.6%). Calf hypertrophy was noted in 53.5% of LGMD and 57.1% of SGPs, extensor digitorum brevis hypertrophy in 42% of LGMD and 35.7% of SGPs, winging of scapula in 39.2% of the LGMD group and 35.7% of the SGPs, valley sign in 28.5% of the LGMD group and 21.4% of the SGPs. Hip abductor sign was positive in 71.4% of LGMD and 64.2% of SGPs. Differential weakness of knee flexors was more common in SGP (57.1%). The mean creatine phosphokinase (CK) value was 2519IU/L and was elevated in 92.8% patients. Muscle biopsy showed a dystrophic pattern in 75% of LGMD and a myopathic pattern in the remaining. Symptomatic cardiac involvement was seen in one patient. ECG changes were seen in 44% of LGMD patients and 50% of the SGP. The common changes noted were T wave inversion in V1, V2 (16%), left ventricular hypertrophy LVH (12%) and right bundle branch block (RBBB) in 12% of the LGMD group. CONCLUSION: Sarcoglycanopathy is a more frequent form of LGMD whereas alpha type is the most common among the SGP. The four types of SGP do not differ in the pattern of muscle involvement. A relatively earlier onset, selective weakness of knee flexors and a very high CK may help differentiate SGP from other forms of LGMD. Immunohistochemistry is very useful in classifying the different types of LGMD prior to genetic analysis.

Magnetic resonance imaging in rabies.

Rabies encephalitis has a classical clinical presentation and its diagnosis is unmistakable. In about a fifth of cases rabies occurs as its paralytic form, which lacks the classic symptoms and may mimic other diseases, especially acute disseminated encephalomyelitis (ADEM). Magnetic resonance imaging of the brain in rabies shows a distinct abnormal pattern that differentiates it from ADEM. Hence it may be a useful tool in diagnosis of paralytic rabies. Failure to administer post-exposure rabies immunoglobulin along with the rabies vaccine may result in vaccine failure.

Recurrent Miller fisher syndrome: a case report.

Miller fisher syndrome (MFS) is a variant of Guillain-Barre syndrome characterized by the triad of ophthalmoplegia, ataxia and areflexia. Recurrences are exceptional with MFS. A case with two episodes of MFS within four years is reported. He presented with findings of ophthalmoplegia, ataxia, areflexia, and oropharyngeal weakness and mild distal sensory impairment during both episodes. Electrophysiological findings showed reduced compound muscle action potentials and sensory nerve action potentials with no evidence of conduction blocks. Nerve biopsy showed segmental demyelination. MRI of brain was normal. He responded well to immunoglobulins during both episodes suggesting that immunomodulating drugs have a role in the treatment of MFS.

Encysted haematoma in a cerebello-pontine angle.

A young primi-gravida with pre-eclamptic toxaemia underwent an elective caesarean at 38 weeks. On 10th day of delivery, she suddenly developed symptoms and signs of right cerebello-pontine angle lesion. On investigation a haematoma with a fluid level could be identified. Coagulation parameters were deranged and blood culture grew coagulase negative staphylococcus aureus. Possible causes of intracranial haematoma at such an unusual location are discussed.

Sequestrated lateral ventricle due to tuberculosis.

A twenty-six year man presented with a short history of raised intracranial pressure. He had papilloedema and long tract signs in both the lower limbs. CT scan of the head revealed unilateral dilatation of the right lateral ventricle. Ventriculography showed block of right foramen of Mono. Patient was treated by right vrentriculoperitoneal shunt and antitubercular drugs. However symptoms recurred within six weeks. MRI done at this stage revealed a sequestrated left lateral ventricle with dilatationof the cut off part of the ventricle. CSF findings were suggestive of tubercular pathology. Such a pathological manifestation has described only once before. The pathogenesis and management is being discussed.

Streptokinase induced primary intraventricular haemorrhage.

Primary intraventricular haemorrhage secondary to thrombolytic therapy has not been reported. A 55 years male who received i.v. streptokinase (STK) followed by heparinization for an acute myocardial infraction developed an extensive primary intraventricular haemorrhage from which he made an uneventful recovery over the next three months.

Delayed onset generalised dystonia after cyanide poisoning.

A 27 year old female developed delayed onset of persistent generalized dystonia following a suicidal attempt with potassium cyanide. Cranial CT scan showed bilateral putaminal hypodensities which were also seen on MRI scans to be hypointense on T1 and hyperintense on T2 weighted images. Multimodality evoked potentials were normal. An improvement was noted with levodopa.

Hemiballismus due to an ipsilateral striatal haemorrhage: an unusual localization.

Hemiballismus has been correlated clinico-anatomically with lesions of the contralateral side, most commonly of the subthalamic nucleus. Hemiballismus due to an ipsilateral lesion is extremely rare. We report the case of a 55 year old female who developed a right sided hemiballismus due to a right striatal haemorrhage, which simultaneously caused a left hemiplegia. The hemiballismus subsided on treatment with dopamine-blockers over the next two weeks.