The safest viral vector system for gene therapy is based on recombinant adeno-associated virus (rAAV) up to date in Phase I clinical trials, which has been developed rapidly and applied for ischemic stroke gene therapy in animal experiments since the past seven years. rAAV vector has made great progress in improving gene delivery by modification of the capsid and increasing transgene expression by encapsidation of double-stranded rAAV genome. And in all, nine therapeutic genes in 12 animal studies were successfully delivered using rAAV vector to ischemic brain via different approaches in rat or mice stroke models for gene therapy and the results suggested that rAAV could mediate genes' expression efficiently; most of them displayed evidently therapeutic efficacy with satisfactory biological safety. Gene therapy involving rAAV vector seems effective in attenuation of ischemic damage in stroke and has greatly promising potential use for patients in the future. In this review, we will focus on the basic biology and development of rAAV vector itself as well as the recent progress in the use of this vector for ischemic stroke gene therapy in animal experiments.

Context: Speech abnormalities are common to the three Parkinsonian syndromes, namely Parkinson's disease (PD), progressive supranuclear palsy (PSP) and multiple system atrophy (MSA), the nature and severity of which is of clinical interest and diagnostic value. Aim: To evaluate the clinical pattern of speech impairment in patients with PD, PSP and MSA and to identify significant differences on quantitative speech parameters when compared to controls. Design and Setting: Cross-sectional study conducted in a tertiary medical teaching institute. Materials and Methods: Twenty-two patients with PD, 18 patients with PSP and 20 patients with MSA and 10 age-matched healthy controls were recruited over a period of 1.5 years. The patients were clinically evaluated for the presence and characteristics of dysarthria. This was followed by quantitative assessment of three parameters: maximum phonation time (MPT), semantic fluency and reading speed. The outcome measures were compared between the patient groups and with controls. Results: Patients with PD had hypophonic monotonous speech with occasional rushes of speech while patients with MSA and PSP had mixed dysarthria with ataxic and spastic elements respectively. All quantitative parameters were affected when compared to controls ( P values <0.001, 0.012 and 0.008 respectively). Maximum phonation time was significantly less in PSP when compared to MSA and PD ( P =0.015). Reading speed also showed a similar trend which was not statistically significant. Semantic fluency was comparable in all three groups. Conclusion: Dysarthria in PD, PSP and MSA have many overlapping but certain distinctive features as well which could serve as a diagnostic clue. Patients with PSP had profound speech impairment probably indicative of the more severe frontostriatial pathology.

Context: Hemispherotomy is a surgical procedure for hemispheric disconnection. It is a technically demanding surgery. Our experience is presented here. Aims: To validate and compare the two techniques for hemispherotomy performed in patients with intractable epilepsies. Settings and Design: A retrospective study 2001-March 2007: Nineteen cases of hemispherotomies from a total of 462 cases operated for intractable epilepsy. Materials and Methods: All the cases operated for intractable epilepsy underwent a complete epilepsy surgery workup. Age range 4-23 years (mean 5.2 years), 14 males. The seizure frequency ranged from 2-200 episodes per day; four were in status; three in epilepsia partialis continua. The pathologies included Rasmussen's, hemimegelencephaly (unilateral hemispheric enlargement with severe cortical and subcortical changes), hemispheric cortical dysplasia, post-stroke, post-traumatic encephalomalacia and encephalopathy of unknown etiology. The techniques of surgery included vertical parasaggital approach and peri-insular hemispherotomy. Neuronavigation was used in seven cases. Results: Class I outcome [Engel's] was seen in 18 cases and Class II in one assessed at 32-198 weeks of follow-up. The four patients in status epilepticus had Class I outcome. Four patients had an initial worsening of weakness which improved to preoperative level in five to eight weeks. Power actually improved in three other patients at 32-36 weeks of follow-up, but hand grip weakness persisted. In all the other patients, power continued to be as in preoperative state. Cognitive profile improved in all patients and 11 cases returned back to school. Conclusions: Both techniques were equally effective, the procedure itself is very effective when indicated. Four of our cases were quite sick and were undertaken for this procedure on a semi-emergency basis.

Objective: Using a fiber-dissection technique, our aim is to study the fiber bundles of the optic radiation. We focused on the course, the length, anatomical relations with lateral ventricle and the relevance of these finding during surgery in the region. Materials and Methods: Five previously frozen and formalin-fixed cadaveric human brains were used. The dissection was done using the operating microscope. Fiber dissection techniques described by Klingler were adopted. The primary dissection tools were handmade, thin, and wooden and curved metallic spatulas with tips of various sizes. Lateral and inferior temporal approaches were made and the optic fiber tracts were dissected. Results: Resections that extend through the roof of the temporal horn more than 30 mm behind the temporal pole cross the Meyer's loop. In the middle temporal gyrus approach, resection that is taken through the lateral wall of the temporal horn more than 55-60 mm behind the temporal pole may cross the optic radiation during their course here on the lateral wall. Conclusion: The presented fiber dissection study clarifies the relationship of optic radiation. Such fiber dissection studies are only few in the literature.

Background: There has been sparse description of cortical dysplasias (CDs) causing intractable epilepsy from India. Aim: Clinical retrospective study of CDs causing intractable epilepsy that underwent surgery. Materials and Methods: Fifty-seven cases of CDs reviewed (1995 till July 2006) are presented. All patients had intractable epilepsy, and underwent a complete epilepsy surgery workup (inter ictal electroencephalography (EEG), video EEG, MRI as per epilepsy protocol, SPECT {interictal, ictal with subtraction and co-registration when required}, and PET when necessary). Surgical treatment included a wide exposure of the pathology with a detailed electrocorticography under optimal anesthetic conditions. Mapping of the sensori-motor area was performed where indicated. Procedures included resection either alone or combined with multiple subpial transactions when extending into the eloquent areas. Results: Our study had 28 (49.12%) cases of isolated focal CDs, and 29 (50.67%) with dual pathology. Average age at the time of onset of seizures in our series was 7.04 years (three months to 24 years), and average age at the time of surgery was 10.97 years (eight months to 45 years). Among coexistent pathologies, one had associated MTS, 16 had coexistent gangliogliomas and 12 (dysembryonic neuroepithelial tumor) DNTs. At an average follow-up of 3.035 years (range 5-10 years), three patients were lost to follow-up. Fifty-one per cent (29/57) patients had a good outcome (Engel Grade I) and 26%(15/57) had a Grade II outcome. Conclusion: Cortical dysplasias have a good outcome if evaluated and managed with concordant electrical and imaging modalities.

Objective: A novel method of treatment of basilar invagination that involves distraction of the atlantoaxial joint using specially designed spiked spacers is described. Bone graft that is additionally placed within the appropriately prepared atlantoaxial joint and posterior to the arch of atlas and lamina of C2 provides bony fusion. Materials and Methods: Between December 2002 and April 2007, 11 patients underwent the discussed method of fixation at the Department of Neurosurgery, King Edward Memorial Hospital in Mumbai, India. All 11 patients had "congenital" basilar invagination and the symptoms were progressive in nature. Results: The mean follow-up period was 21 months (range 8-40 months). Neurological improvement and successful distraction with atlantoaxial stabilization and ultimate bone fusion was achieved in all the patients and was documented with dynamic radiography. There were no neurological, vascular, or infective complications. Conclusions: We conclude that the described method of atlantoaxial joint distraction and fixation provides an alternative treatment strategy for cases with basilar invagination. "Joint distraction" as a stand-alone method could provide reduction of basilar invagination and firm stabilization in such cases.

Background: Epileptic seizures, predominantly or exclusively during sleep had been the focus of attention for many electroencephalographers. Though few epileptic syndromes are associated with sleep seizures (SS) its frequencies in Indian patients is still unknown. Aim: To find out the patterns of epilepsies in patients having SS and compare them with patients having wake seizures (WS). Setting and Design : Open label hospital based study. Materials and Methods: One hundred and forty-four (13%) patients having predominantly SS were compared with 976 (87%) patients of WS by various clinical, electrophysiological and radiological factors. Statistical Analysis: Chi square test and student T test, using software SPSS (version 10, 1999) was applied to compare various parameters. Relative risk was calculated by 2 x 2 contingency table. Results: The seizure semiology was better defined in patients with WS and GTCS was more common in SS ( P = 0.001). Wake-electroencephalogram (EEG) was abnormal in significantly ( P = 0.001) higher number of patients with WS. Symptomatic etiologies were found in more than half patients. Left lobe involvement was more common in patients having SS ( P = 0.000). After symptomatic, idiopathic generalized and frontal lobe epilepsy were most frequent with SS. Undetermined epilepsy was found in 37 (25.7%) patients with SS. Conclusion: Epilepsies associated with SS were less frequent and had symptomatic cause in most cases. Left hemispherical and frontal lobe lesion were more commonly associated with SS. Frontal lobe and idiopathic generalized epilepsy was most frequent in patients of SS. Sleep EEG should always be done in patients with sleep seizures.

Background and Objectives: This study is designed to understand the pathophysiology of one of the most serious health problems, chronic tension-type headache (CTTH). Two polymorphic sites in serotonin transporter protein gene attracted much interest. These are: the variable number of tandem repeats (VNTR) and 5'-flanking promoter region (5-HTTLPR). Materials and Methods: VNTR and 5-HTTLPR polymorphisms were investigated in 126 CTTH patients and 138 healthy control subjects. The patients were being treated with amitripytyline or citalopram or sertraline (SSRI). The polymerase chain reaction (PCR) method was used to investigate the polymorphisms in the serotonin transporter protein gene. Results: There were no statistically significant results based on the 5-HTTLPR gene alleles, however, STin 2.12/12 genotype and STin 2.12 allele were seen to predominate the control group. In order to investigate the combined effect of the two polymorphic loci on the 5-HTT gene expression, samples were separated into nine groups. Genotypes (S/S-12/10) and (L/S-12/10) displayed statistically significant frequency in the CTTH group than in the control group. No significant differences were noticed between the 5-HTTLPR and VNTR haplotype groups and success in treatment. Conclusion: It is possible to make reliable comparisons and hypothesis about the homozygous and/or heterozygous presence of S and STin 12/10 alleles which may be in interaction with CTTH. On the other hand, the presence of homozygous L and STin12 alleles may play a protective role against CTTH. It is also possible that heterogeneity among diseases showing the same clinical research will require a lot of effort for individual identification.

Background: Alzheimer's disease (AD) is suspected to be currently under-diagnosed in India, thus the need for a brief, effective screening test for the condition. Aims: We aimed to test the Malayalam translation of the 7-Minute Screen (7MS) for detecting those at high risk for AD and to report on the subscores used to derive the Alzheimer's risk score. Setting and Design: This study was performed in Kerala State amongst young university students and elders in residential care homes. Materials and Methods: Two hundred and eighty-two volunteers were tested, 178 young controls (aged 20-29) and 104 literate elders, (55-92 years). None were clinically diagnosed with AD. Statistical Analyses: Elders and controls were assessed as High or Low AD Risk with the published 7MS algorithm. Performance was compared between groups with ANOVA. Results: The algorithm estimated high (n = 61/104) or low (n = 40/104) AD risk in the elderly. Significant differences were found between controls, low- and high-risk groups on all four components of the screen (Orientation: F = 131.1, Enhanced Cued Recall: F = 23.4, Clock Drawing: F = 65.1, Verbal Fluency: F = 15.7, P < 0.0001 for all) and in the risk scores (F = 144.7, P < 0.0001). Age and gender affected verbal fluency, orientation and clock drawing performance. The high-risk group had worse scores for orientation and better scores for memory than previously reported for AD cases in other populations. Conclusions: The 7MS may be a useful screening test for cognitive impairment in India. Suggestions are given for revising the 'risk algorithm' for more appropriate AD risk assessment in this population.

Background: Scalp is the most common site of soft tissue arteriovenous fistulae and surgical excision has been the primary mode of treatment. Endovascular treatment has evolved as an alternative to the surgery. Aims: To evaluate the effectiveness of percutaneous direct-puncture embolization of cirsoid aneurysms. Materials and Methods: From January 1995 to December 2004, 15 patients underwent percutaneous direct-puncture embolization of cirsoid aneurysms. Plain X-ray, computerized tomography scan and complete selective cerebral angiogram were done in all. Seven patients had forehead lesions, four had temporal and the remaining four patients had occipital region cirsoid aneurysms. Lesions were punctured with 21-gauge needle and embolized with 20-50% cyanoacrylate-lipiodol mixture. Circumferential compression was applied during injection. Results: Post-embolization angiogram showed complete obliteration in 11 patients. The remaining four patients required adjunctive transarterial embolization with polyvinyl alcohol particles for complete lesion devascularization. Two patients had post procedure surgery for removal of disfiguring and hard glue cast. There were no major procedure-related complications. No patients had any recurrence in the follow-up. Conclusion: Percutaneous direct puncture embolization of cirsoid aneurysms is a safe and effective procedure. It can be effectively used as an alternative to surgery. Sometimes adjunctive transarterial embolization is also required to deal with deeper feeders.

Background: Clinical outcome of internal carotid artery (ICA) occlusion is highly variable and the reason is uncertain. Aim: To study the predictive factors of clinical outcome and stroke recurrence in patients with ischemic stroke associated with unilateral atherosclerosis-related ICA occlusion. Settings and Design: Prospective study in neurology department of a single hospital. Materials and Methods: We prospectively studied 66 patients who suffered from first-ever ischemic stroke associated with unilateral atherosclerosis-related ICA occlusion over a period of two years. The end point was death or stroke recurrence. Statistical Analysis: Chi-square or Fisher's exact test was used to analyze predictors of early functional outcome. Multivariate analysis was used to analyze predictors of death or stroke recurrence within two years. Result: Higher age (³70 years) predicted a worse functional outcome ( P = 0.049). Total anterior circulation syndrome (TACS) was associated with a poor functional outcome ( P < 0.001), but lacunar syndrome had a better outcome ( P = 0.001). Stroke in evolution predicted a poor outcome ( P = 0.001), while those with symptom improvement had a better outcome ( P = 0.016). Pneumonia predicted a poor outcome ( P = 0.021). Five patients expired and 22 patients suffered from recurrent stroke in the following 24 months. Previous transient ischemic attack (TIA) and anemia were associated with a higher risk of death or recurrent stroke within two years ( P = 0.036, P = 0.012). Conclusion: High age, TACS, stroke in evolution and pneumonia were predictors for poor functional outcome. Previous TIA and anemia were predictors for death and recurrent stroke within two years.

A 72-year-old man who had undergone nephrectomy for left renal cell carcinoma (RCC) presented with worsening of cognitive function and frequent loss of consciousness. Computed tomography (CT) revealed tumor mass in the third ventricle and hydrocephalus. A ventriculoperitoneal (VP) shunt was placed to treat the hydrocephalus. The postoperative course was uneventful, and he was followed closely without aggressive therapy. Four months after surgery, the tumor expanded rapidly due to intratumoral hemorrhage and he died due to sepsis. The autopsy findings revealed a solitary metastatic RCC in the third ventricle, with massive intratumoral hemorrhage. Solitary metastasis of RCC to the third ventricle is quite rare and difficult to treat. The case report highlights that early diagnosis and treatment are critical, even in slowly progressive RCC patients, because of the possibility of intratumoral hemorrhage.

A 35-year-old female with migraine without aura, presented with sudden onset of visual aura along with loss of vision on the left side. Following this she had nausea, vomiting and headache. Magnetic Resonance Imaging (MRI) performed at this stage revealed ill-defined lesions hyperintense on Flair images, located in the right temporal and right occipital region. Diffusion weighted images, MR angiogram, T1-weighted and T2-weighted images were normal. She got relief with symptomatic treatment. Twenty days after this attack of migrainous aura she had a similar episode. An MRI scan was performed again. It revealed similar lesions only in the right occipital lobe. Follow-up MRI performed seven weeks later was normal.

Aspergillus sellar abscess is a very rare form of fungal infections of the central nervous system (CNS). In this report, we describe the successful treatment of a patient with aspergillus sellar abscess. A 65-year-old woman presented with headache, nasal discharge and decreased visual acuity. The diagnosis of sellar mass was made on the basis of magnetic resonance imaging (MRI) examination. The computed tomography (CT) scan revealed sellar enlargement and sellar floor bony destruction. After hospitalization the patient underwent transsphenoidal surgery. Histopathological examination of the sellar mass revealed aspergillosis. Postoperatively, amphotericine-B and itraconazole therapy was started. During a six-month follow-up, the patient's headache and inertia disappeared, visual acuity improved. Aspergillus sellar abscess must be considered in the differential diagnosis of a sellar mass. The correct diagnosis of pituitary aspergillosis can only be achieved by histopathological examination. Surgical intervention and antifungal therapy should be considered the optimal treatment.

Toxoplasmosis is a common opportunistic infection in patients with AIDS in whom it frequently presents as intracranial space-occupying lesions. In the immunocompetent patient the most common manifestation is as asymptomatic cervical lymphadenopathy which may be associated with vague systemic manifestations such as fever or myalgia. In very rare cases people with normal immunity may present with meningoencephalitis polymyositis or myocarditis. It is very rare to encounter a brainstem granuloma due to toxoplasma infection in such patients. We report a non-immunocompromised man who presented with multiple cranial nerve palsies due to a brainstem lesion, which turned out to be a toxoplasma granuloma. He recovered completely after a four-week course of Pyrimethamine and Sulphadoxine. An extensive search of the literature failed to reveal any prior reports of a similar nature. This case is being reported because of its rarity and the complete recovery made by the patient.

Insulinoma presents with myriad manifestations and severe neurological deficit may develop due to delay in diagnosis. We report a lady who presented with Glasgow coma scale of E1 M2 V1, which did not improve after correction of hypoglycemia. There was complete reversal of neurological deficit and brain magnetic resonance imaging changes of hypoglycemia on follow-up after resection of pancreatic insulinoma. This is the first report which shows reversal of hypoglycemic changes in MRI after resection of insulinoma. Insulinoma, pre and post surgery provides a model for study of the effect of hypoglycemia and its improvement after euglycemia.

We report a 29-year-old man with a unique presentation of vasculitis as acute unilateral subdural effusion and meningoencephalitis. Magnetic resonance imaging showed a brainstem lesion that spread to the thalamus over time. There were no systemic features of vasculitis other than a positive pathergy test. Histopathological examination from the pathergy site showed neutrophilic infiltrate and leucocytoclastic vasculitis. The condition was steroid responsive and he remained in remission at two years' follow-up. The anatomy of the brainstem lesion, absence of other inflammatory and infective conditions on evaluation suggests a vasculitic pathology either as primary central nervous system angiitis or as neurological presentation of systemic vasculitis like Behηet's disease although the international diagnostic criteria for Behηet's were not fulfilled.

Chronic lymphocytic leukemia (CLL) is a frequent hematological malignancy, with meningeal or peripheral nerve infiltrations being the most commonly encountered neurological complications. In this report, we describe a CLL patient with Miller-Fisher syndrome (MFS) who responded to immune modulation with plasmapheresis. A 47-year-old man diagnosed as B-cell CLL admitted with neutropenic fever. He complained of diplopia and numbness of both arms. Neurological examination revealed a bilateral external ophthalmoplegia, dysphagia, dysarthria, mild shoulder girdle muscle weakness and gait ataxia, accompanied by absent tendon reflexes. Nerve conduction studies were indicative of a predominantly axonal sensori-motor peripheral neuropathy. This association of CLL with MFS had not been previously reported in the literature.

Neurological complications of hemolytic anemias are rather uncommon. We are reporting two cases of hemolytic anemia presenting as chorea and recurrent ischemic stroke. The first one is a case of chorea in a patient with sickle cell trait. Reviewing the literature we could find only one case report of chorea in sickle cell disease disease. The second is a case of recurrent ischemic stroke in hereditary spherocytosis. We could trace two reports on a Medline search, though their association was less certain.