"I swear, I can't stop it!" - A case of severe Tourette's syndrome treated with deep brain stimulation of anteromedial globus pallidus interna.

INTRODUCTION: Tourette's syndrome (TS) is a complex neuropsychiatric disorder characterized by the presence of multiple motor and vocal tics. Here, we report the case of a young man with severe TS refractory to multiple medications who underwent deep brain stimulation (DBS), which was successful in substantially ameliorating his tics. To our knowledge, this is the first such report from India and South Asia. CASE REPORT: An 18-year-old right-handed male patient was diagnosed with TS at the age of 10 years. He had facial and ocular tics. He was also hitting his fist against his chest and shouting obscenities. The manifestations would be present in every waking hour with a maximum tic free interval of 15-20 minutes. They would often result in self-injury or damage to objects. He would have frequent crying spells, anger outbursts, and death wishes. As tics became highly conspicuous and socially inappropriate, he dropped out of school and remained almost completely house-bound for the preceding year. On evaluation, he scored 96 (46 on tic-severity subscale and 50 on impairment subscale) of a maximum of 100 on the Yale Global Tic Severity Scale. (YGTSS). MANAGEMENT: After failure of multiple combinations of medicines, repetitive transcranial magnetic stimulation, and behavioural therapies, he successfully underwent DBS to bilateral anteromedial globus pallidus interna. CONCLUSION: Tic severity reduced substantially post-surgery, with the YGTSS score improving by more than 72%. These improvements were sustained on follow-up visits with the patient successfully returning to join college. To our knowledge, this is the first such report from India and South Asia.

Association of oral-facial-digital syndrome type VI (Varadi-Papp syndrome) with optochiasmatic pilocytic astrocytoma.

INTRODUCTION: Varadi-Papp syndrome (VPS) or oral-facial-digital syndrome type VI (OFDS-VI) is a rare autosomal recessive disorder distinguished from other OFDSs by metacarpal abnormalities with central polydactyly and by cerebellar abnormalities. It can be associated with central nervous system tumors, which most commonly has been a hypothalamic hamartoma. CLINICAL CASE REPORT: The boy had unusual facial features, developmental delay, limb malformations, and other phenotypic anomalies suggestive of VPS. X-ray of the hand and feet showed right hand polydactyly. He also had a deep wider peduncular fossa, thickened superior cerebellar peduncle, and inferior vermian hypoplasia along with optochiasmatic tumor. The patient underwent a right pterional craniotomy and tumor decompression. Histopathology was suggestive of a pilocytic astrocytoma. CONCLUSION: This is the first case in available literature in which the OFDS-VI has been associated with an optochiasmatic pilocytic astrocytoma. We suggest an expansion of the disease spectrum of OFDS-VI to include the association of optochiasmatic pilocytic astrocytoma.

Rosette-forming glioneuronal tumor -- evidence of stem cell origin with biphenotypic differentiation.

Rosette-forming glioneuronal tumor (RGNT) of the fourth ventricle is a new addition to the WHO classification of central nervous system tumors. To date, 72 cases have been described in literature. In the present study, we report the clinical and imaging features, with detailed histopathological and immunohistochemical profile, of eight cases. Confocal microscopic evidence of stem cell origin with biphenotypic, glial and neurocytic differentiation is presented with a comprehensive review of literature.

Does CSF composition predict shunt malfunction in tuberculous meningitis?

BACKGROUND: Hydrocephalus secondary to tuberculous meningitis (TBM) continues to be a challenging condition to treat for neurosurgeons in developing countries. Shunt complications are reportedly more frequent in patients undergoing ventriculo-peritoneal shunt in patients with TBM than in those undergoing shunt surgeries for other causes. AIM: The aim of this study was to evaluate the relationship of cerebrospinal fluid (CSF) composition on shunt malfunction. METHODS: We compared the CSF composition of 53 patients who had shunt malfunction during a five year period with that of 137 matched controls. RESULTS: Patients who had shunt malfunction had a significantly higher concentration of CSF protein. The CSF cellularity and glucose concentration did not have any significant bearing in predicting shunt malfunction. Patients with CSF protein concentration of more than 200 mg/dL had a four times higher risk of having shunt malfunction than those with a concentration of less than 100 mg/dL. Patients with CSF protein in the 100-200 mg/dL range represent an intermediate zone. CONCLUSION: To conclude, patients with CSF protein concentration of more than 200 mg/dL have a significantly higher risk of shunt malfunction and hence have to be followed up closely.

Cerebral coenurosis mimicking hydatid disease - report of two cases from South India.

Coenurosis, a rare zoonotic disease caused by the larval form of Taenia multiceps (bladderworm) is common in sheep rearing countries, but human infections are rare. Central nervous system involvement produces large giant sized cysts that radiologically closely mimic hydatid cysts. Most human infections resulting in cerebral coenuri have been reported from Europe and Africa. We report two cases of cerebral coenurosis from India, the first in a 55-year-old male presenting with a large cystic lesion in the right parietooccipital region and the second occurring in a 36-year-old male involving the left temporal trigonal region, that radiologically closely mimicked hydatid cyst. Histopathologic examination revealed characteristic features of coenuri with multiple protoscolices invaginating into a large cyst lined by outer cuticular layer. Awareness of this rare parasitic infestation is important to discriminate from the more common hydatid and giant cysticercal cysts.

Short-term exposure of multicellular tumor spheroids of a human glioma cell line to the glycolytic inhibitor 2-deoxy-D-glucose is more toxic than continuous exposure.

The glycolytic inhibitor 2-deoxy-D-glucose (2-DG) has been used as a therapeutic agent and as an adjuvant in cancer therapy with either weekly fractions of the treatment or daily administration. While the weekly fraction has often been found to be nontoxic and effective, other treatment regimes are tolerated to a relatively lesser extent. It was therefore, considered worthwhile to investigate the efficacy of short- and long-term exposure of tumor cells to 2-DG under the controlled conditions. Seven-day-old MTS were exposed to 2-DG (5 mM, equimolar to glucose concentration in media) for different time intervals (30 min to 24 h) trypsinized and plated for clonogenicity. Alternatively, spheroids were grown either continuously in the presence of 2-DG or were treated with 2-DG for 2 h (short-term exposure) and grown in 2-DG-free media for 21 days and assessed for spheroid growth, cell viability, apoptosis, cytogenetic damage, mitochondrial status, and oxidative stress. Exposure of spheroids to 2-DG for 2-4 h induced 30% cell death (SF 0.70) while, a 24-h exposure resulted in only a marginal decrease in clonogenicity (SF 0.95). Furthermore, the spheroids disintegrated completely by 28 days in the case of 2-h exposure to 2-DG, while spheroids grown continuously in the presence of 2-DG repopulated. The cytotoxicity following short-term exposure of MTS to 2-DG was primarily due to the induction of apoptosis revealed by morphological features as well as flow cytometric analysis of the DNA content. Interestingly however, cytogenetic damage (micronuclei induction) was observed in spheroids that were continuously exposed to 2-DG. Short-term exposure to 2-DG resulted in a significant increase in ROS levels and a reduction in the levels of unoxidized cardiolipin as measured by NAO suggesting the involvement of mitochondria leakiness leading to oxidative stress which, could be responsible for apoptotic cell death observed under these conditions. However, continuous exposure to 2-DG resulted in a moderate level of oxidative stress leading to the genomic instability. Preliminary studies also show that spheroids exposed continuously to 2-DG result in the development of resistance to certain chemotherapeutic drugs which could be correlated with elevated levels of mdr1. The present results suggest that a persistent down-regulation of glycolysis (as seen here with continuous exposure to 2-DG) could activate prosurvival responses besides inducing moderate levels of oxidative stress resulting in the development of resistance against therapeutic agents.

Multiple neural tube defects: a clinical series of seven cases and their embryological basis.

INTRODUCTION: There have been isolated cases of such multiple neural tube defects (MNTDs) described in the world literature. We report 7 cases of MNTDs and review the available literature. MATERIALS AND METHODS: This retrospective study included all patients who were managed with MNTDs at our institute from 2001 to 2006. RESULTS: Among a total of 474 cases of neural tube defects,7 patients had MNTDs. Among these, 5 had a double neural tube defect while 2 had a triple neural tube defect. Six were operated upon successfully while 1 patient refused any form of intervention. CONCLUSION: The presence of meningomyelocele and/or encephaloceles at multiple (two or more) sites along the vertebral axis is a very rare event occurring in <1% of cases. Less than 10 cases have been described in the published literature. This series is the largest so far on these rare anomalies. We also discuss the embryogenesis, which is better explained by the multisite closure theory.

Intraspinal hemangioblastoma: analysis of 22 cases.

Hemangioblastomas of the spinal cord are relatively uncommon benign tumors. The purpose of this study was to evaluate the clinical features, management strategies and outcomes in patients with spinal hemangioblastomas. We retrospectively analyzed 22 patients who were operated on for spinal hemangioblastoma at the All India Institute of Medical Sciences, New Delhi, India. In our center, 113 patients with hemangioblastomas had been managed over a 14-year period (1992-2006). Ninety-one of these hemangioblastomas were intracranial and 22 were intraspinal. The average age of patients was 35.9 years. The most common location was the cervical region. The most common presenting feature was progressive compressive myelopathy (22 patients). An associated syrinx was seen in 87% of cases. Gross total resection was achieved in all patients. All but two improved or stabilized with respect to their preoperative neurological status. This is one of the larger series in the literature on spinal hemangioblastoma. We discuss the modes of presentation, surgical management strategies and excellent functional outcome after microsurgical excision.

Cervical meningomyelocele--an institutional experience.

OBJECTIVE: Cervical myelomeningoceles (CMMC) are a less common but distinct subgroup of myelomeningoceles. Their embryology and clinical characteristics vary from the more common thoracolumbar variant. Only a few small series have been published addressing this lesion in the literature with the largest one of them addressing nine patients. The authors present one of the largest series of cervical myelomeningoceles, review their embryology, clinical features, and their management strategies. METHODS: This study included all the children who were managed for cervical myelomeningocele between Jan 2001 to July 2006 at our center. RESULTS: There were a total of ten children (five boys and five girls) operated on for cervical myelomeningoceles. The ages ranged between 2 months to 14 months. Neurological examination was normal in majority of the children with absence of gross orthopedic deformity in all the children. Three patients had associated hydrocephalus, two had Chiari malformation, and four of them had a syrinx. Surgical excision of the sac was performed for all. CONCLUSION: Cystic dysraphisms of the cervical differ embryologically, clinically, and structurally from thoracolumbar meningomyelocele and have a more favorable outcome. A good pre operative evaluation is recommended to assess any associated anomalies and identify the internal structures. Surgery excision of these lesions with intradural exploration of the sac to release any potential adhesion bands as well as other associated anomalies is recommended.

Neuronavigation in a developing country: a pilot study of efficacy and limitations in intracranial surgery.

CONTEXT: Neuronavigation provides a patient-specific, three-dimensional (3-D) anatomy for preoperative planning and intraoperative navigation. However, the initial and maintenance costs are quite prohibitive, especially in the Indian scenario. AIMS: To study the efficacy and limitations of neuronavigation, especially in the Indian scenario. SETTINGS AND DESIGN: A prospective nonrandomized study. MATERIALS AND METHODS: A total of 121 patients underwent intracranial surgery from 2002-2006, in which neuronavigation was used. In this, the initial part, we studied the efficacy and limitations of neuronavigation in the initial 37 patients. The efficacy of the image guidance was graded according to a point's scale in which points were awarded ranging from 0 to 3. Cranial image guided score (IGS) was calculated by the summation of grading during designing the flap/burr hole, delineation of the intraoperative anatomy, navigation and access to the lesion and resection / biopsy of the lesion or completion of the procedure. The scoring ranged from 0-12 and the utility of IGS in cranial neurosurgical procedures was calculated based on the total points for each surgery. RESULTS AND CONCLUSION: Cranial image guidance was useful in a variety of operative steps. Intraoperative approach and navigation was relatively easier with an increase in perception of safety. Limitations of IGS include learning curve, cost and the phenomenon of brain shift. Drawbacks of the study included that this was a subjective rather than a truly objective study and the relatively lesser number of patients. We hope to conduct a larger study with randomization but the question of ethical approval would be a primary concern.

Aplasia cutis congenita of the scalp: therapeutic modalities.

Agenesis of scalp is an uncommon but well-recognized clinical entity. Congenital scalp and skull defects can be either obvious or occult; over 300 cases have been reported in literature. Aplasia cutis congenita (ACC) is recognized as a heterogeneous disorder, all characterized by focal absence of the epidermis, dermis and sometimes the calvarium and/or dura. We present a case of ACC in an infant whose mother was exposed to a teratogenic drug (Methimazole--an antithyroid drug) during pregnancy. This case report is presented to highlight the steps to successful management. Definitive full thickness scalp cover at the earliest avoids secondary infection, eschar formation and exsanguination.

Spontaneous spinal extradural hematomas.

We review three patients who presented with acute spontaneous spinal extradural hematomas (SSEH). We discuss the presentation, imaging and management strategies. All three patients were adult women with thoracic SSEH. All had motor weakness prior to surgery. One patient recovered completely, one partially recovered and one did not recover. SSEH, although rare, should be considered in cases of acute onset paraparesis. The diagnostic modality of choice is magnetic resonance imaging. Favourable outcome is related to aetiology, interval between the ictus and presentation, and the severity of the neurological deficits. Emergent surgical drainage is the treatment of choice.

Endoscopic assisted excision of a retroclival arachnoid cyst presenting as hysterical breathlessness.

BACKGROUND: Arachnoid cysts are benign developmental cysts occurring most commonly in the middle fossa. Posterior fossa arachnoid cysts are less common, with retroclival arachnoid cysts especially in the pediatric age group being rare. PATIENTS AND METHODS: We present a case of a retroclival interpeduncular farachnoid cyst in a 10-year-old boy who presented with left-sided ptosis and episodes of hysterical breathlessness. RESULTS: The surgical treatment involved endoscopic assisted microsurgical excision of the cyst and the child made an uneventful and complete recovery with complete cessation of breathlessness. The clinical presentation, etiopathogenesis, imaging characteristics and treatment modalities are discussed and the relevant literature reviewed.

Primary plasma cell granuloma of petrous bone.

Plasma cell granulomas are rare intracranial lesions that can mimic a variety of intracranial tumours. As they are usually benign lesions, their identification assumes importance. We report a case of plasma cell granuloma in a 52-year-old man presenting with features of left sided V, VII and bilateral VIII nerve involvement who underwent subtotal excision of the lesion. The relevant literature is reviewed.

Spontaneous subdural empyema in falciparum malaria: a case study.

CLINICAL HISTORY: Malaria is one of the most common diseases in the tropical countries. Cerebral malaria is usually a diffuse symmetric encephalopathy with focal signs being unusual. METHODS: We present a three-year old girl lapsing into unconsciousness following a seizure while undergoing treatment for malaria. Imaging revealed a large heterogenous density, left hemispheric acute subdural haematoma with brain herniation. Investigations revealed anaemia, thrombocytopenia and positive peripheral blood smear for falciparum malaria. RESULTS: Treatment involved surgical evacuation of the clot and the associated subdural empyema, intravenous quinine and antibiotics. CONCLUSION: This is the second case report of spontaneous subdural empyema in complicated falciparum malaria and highlights a rare but surgically manageable complication.

Dynamics simulation of the interaction between the novel intercalator diethidium cation and B-form DNA.

Previous research has described the interaction between the novel molecule diethidium (2,7-diamino 9-[2,7 diamino 10-N-phenanthridium] 10-N-phenanthridium) (Figure 1) and B-form DNA. Our goal is the elucidation of diethidium as the first member of a novel class of drugs which are potential pharmaceutical agents. This class of potential drug molecules differs from previously known intercalators in the following ways: a) Its structure, that of two perpendicular planes, each known to have excellent intercalation properties, is novel b) Unlike known bis-intercalators, the linker region length in diethidium is zero c) The geometry of the drug matches the geometry of the space available in the major groove d) The drug is shown to cause some vectorial disruption of DNA. For this paper, we have performed a series of 200 picosecond dynamics simulations on the complex formed between diethidium in the major groove and a dodecarner of double-stranded B-form DNA, CGCGAATTCGCG, and have shown that this complex has a intricate interaction. The DNA dodecamer is found to be in an intermediate A-B state, but, even in simulations as long as 1 nanosecond, the drug does not back-out or otherwise leave the intercalation site. The drug is found to be mobile within the intercalation site on timescales longer than 1 nanoscale. The mobility of the drug within the intercalation site has been predicted by our previous energy minimization studies.

Site-specific adducts derived from the binding of anti-5-methylchrysene diol epoxide enantiomers to DNA: synthesis and characteristics.

The direct synthesis and characterization of site-specific adducts derived from the binding of (+)-1R,2S-dihydroxy-3S,4R-epoxide-1,2,3,4-tetrahydro-5-methylchrysene and the (-)-1S,2R,3R,4S-enantiomer [(+)- and (-)-5-MeCDE, respectively], to the N2-guanine residues in the oligonucleotide d(CCATCGCTACC) are described. The spectroscopic characteristics of the 5-MeCDE-modified oligonucleotides are discussed, and it is shown that their CD characteristics can be used to distinguish between the trans-addition products of the binding of the (+)- and (-)-enantiomers of 5-MeCDE (C4 position). The 11-mer duplexes with the normal complementary strands are destabilized by the site-specific, covalently bound 5-MeCDE residues: the melting points, Tm, are 5-10 degrees lower than in the case of the unmodified duplex. Stereoselective exonuclease enzyme digestion patterns of the single-stranded (+)- and (-)-trans-5-MeCDE-modified oligonucleotides (Mao et al, 1993, Biochemistry, 32, 11785-11793) were used to probe the orientations of the covalently bound 5-MeCDE residues relative to the modified guanine and the 5'-3' strand polarity; the aromatic residues are positioned either on the 5'-side [(+)-5-MeCDE], or the 3'-side [(-)-5-MeCDE adduct] of the modified guanine residues. The electrophoretic mobilities of the (+)-5-MeCDE-modified 11-mer duplexes in native polyacrylamide gels are slower than those of unmodified and modified duplexes containing the stereoisomeric (-)-5-MeCDE-N2-dG lesions. This indicates that the lesions derived from the tumorigenic (+)-5-MeCDE induce greater degrees of bending or local flexibility than the non-tumorigenic (-)-5- MeCDE enantiomer. These differences in the orientational and structural characteristics are similar to those observed with analogous DNA adducts derived from the tumorigenic (+)-7R,8S-dihydroxy-9S,10R-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene and the non-tumorigenic 7S,8R,9R,10S-enantiomer, respectively. The adducts derived from BPDE and 5-MeCDE enantiomers thus display similar characteristics that depend primarily on the PAH diol epoxide enantiomer stereochemistry. This direct synthesis approach can be used to generate milligram quantities of site-specific 5-MeCDE-modified oligonucleotides that are suitable for NMR studies (Cosman, et al., 1995, Biochemistry, 34, 6247-6260).

Biting behaviour of Armigeres subalbatus (Coquillett) with reference to host selection and landing.

Armigeres subalbatus (Coquillett), a vicious crepuscular biter, has been selected to study the biting behaviour with reference to factors affecting landing and host selection in the laboratory. The mosquito showed a higher attractancy to relatively warmer skin of human hands. There was also a significant attraction towards the artificially warmed hands than the normal ones, and the mosquitoes avoided the artificially cooled hands. Therefore, host temperature is a factor which influences the attraction and subsequent landings of A. subalbatus. When the mosquitoes were offered animal hosts, the order of host preference by these mosquitoes was hen > rabbit > guinea pig, both in single and two-host combinations thus, showing their preference to avian host.

A neural network approach to the early detection of cancer.

Early detection of some cancers (especially of the colon) may be achieved by nuclear magnetic resonance (NMR) spectroscopy applied to whole blood samples. Analysis by conventional Fourier signal processing techniques of the data so obtained has proved to be unreliable because of noise within the associated spectrum. This paper describes a neural network approach to analysis of the NMR data. At the present time, this method has proved to be highly reliable in differentiating between patients with an without colon cancer.

Histopathology of the donor gallbladder removed at orthotopic liver transplantation: correlation with graft function.

The histopathology of 50 consecutive donor gallbladders removed during orthotopic liver transplantation was reviewed and correlated with graft function. Multiple sections of the gallbladders were examined for the presence of mucosal congestion, hemorrhage, and necrosis, without prior knowledge of the clinical outcome. Each pathologic feature was graded as absent (0), involving less than 10% (1+), 10% to 50% (2+), or more than 50% (3+) of the histologically examined mucosa. Graft function was determined by two transplant surgeons, a poor diagnosis being worsening of liver function tests associated with declining mental status and resulting in immediate retransplantation or early postoperative death; all others were categorized as good. Of 39 patients with good graft function, 18 had normal donor gallbladders, 11 had congestion only, and 10 had hemorrhage and/or necrosis. Of 11 patients with poor graft function, eight had hemorrhage and/or necrosis (2+ in seven), three had congestion only, and none had a normal gallbladder mucosa. Congestion alone was found to be a poor predictor of graft damage. Presence of any grade of hemorrhage and/or necrosis in donor gallbladders as related to poor liver graft function had a sensitivity of 73%, a specificity of 74%, a positive predictive value of 44%, and a negative predictive value of 91%. When hemorrhage and/or necrosis of 2+ severity was separately grouped and correlated with poor graft function, the specificity rose to 97% and the positive predictive value to 88%, and the negative predictive value was similar at 90%. We conclude that donor gallbladders often show mucosal abnormalities consisting of varying degrees of congestion, hemorrhage, and necrosis. The finding of hemorrhage and/or necrosis affecting more than 10% of the mucosa appears to be a specific lesion of ischemic damage that correlates highly with poor liver graft function.