Safety and efficacy of donepezil hydrochloride in patients with mild to moderate Alzheimer's disease: Findings of an observational study.

BACKGROUND: Alzheimer's disease (AD), a progressive brain disorder, is the most common cause of dementia among the elderly. Donepezil hydrochloride is a potent, reversible, and highly selective inhibitor of acetylcholinesterase (AChE). It is chemically distinct from other cholinesterase (ChE) inhibitors which are effective in the treatment of AD. OBJECTIVES: To evaluate the safety and efficacy of donepezil hydrochloride therapy over a 12 weeks period in patients with mild to moderate AD in Indian population. MATERIALS AND METHODS: In this post-marketing study, patients with mild to moderate AD received oral donepezil hydrochloride 5 mg/day for 4 weeks followed by 10 mg/day for 8 weeks. Patients were assessed 4 times weekly for cognition on 'Mini Mental Status Examination (MMSE) scale', and function on 'Activities of Daily Living (ADL) index'. Clinicians and caregivers assessment of safety and efficacy was assessed on a 5-point rating scale. RESULTS: One hundred and seventy two of one hundred and eighty two patients completed 12 weeks of study period. MMSE score significantly improved (P<0.0001) from 16.72 at baseline to 19.77 after 12 weeks, and there was significant improvement (P<0.05) in ADL index in 13 of 17 domains after 12 weeks. Caregivers and clinicians rated the therapy as very good to good in >80% and >90% patients, respectively. Adverse events were consistent with the known pharmacological and safety profile of donepezil. CONCLUSIONS: Donepezil is well tolerated in Indian patients with mild to moderate AD with significant improvement in cognition and function.

Cushing's disease: management outcome in a tertiary care centre.

UNLABELLED: Cushing's syndrome (CS) can pose a challenge in diagnosis and management. Successful management of CS needs accurate localization of the site of lesion. Present article narrates experience of a single center dealing with large number of patients with CS and highlights difficulties in diagnosis as well as management of Cushing's disease (CD). METHODS: All patients with CD, where histopathological lesion was documented were studied to evaluate yield from different diagnostic tests. Diagnosis was established by standard 2 days low dose dexamethasone suppression test. Localization of the lesion was achieved with high dose dexamethasone suppression (HDDS) and imaging. Inferior petrosal sinus sampling (IPSS) was used whenever diagnosis was not arrived at with the standard tests. RESULTS: Out of 100 consecutive patients of CS seen, 69 had CD. HDDS had sensitivity of 70% and specificity of 99% in localizing the lesion. Imaging localized the lesion in 68% of patients. Combination of HDDS and imaging localized the lesion in 90% of patients. IPSS helped to localise the lesion in remaining 10% of patients. Transsphenoidal surgery was carried out in 65/69 patients. Cure rate for microadenoma was 77% and for macroadenoma was 36%. Mortality and morbidity rate was 7% and 7% respectively. 2nd TSS, radiotherapy and bilateral adrenalectomy were the additional modalities used in that order, in patients who were not cured or who had recurrence. CONCLUSION: Management of CS is best carried in a center where a team of experienced endocrinologist and neurosurgeon is available.

Cerebellar haemangioblastoma with extensive dissemination.

Haemangioblastomas are benign tumours of uncertain origin. They are composed of capillaries and/or cavernous spaces interspersed with interstitial cells. Malignant spread, distant metastases and subarachnoid seeding are very rare, and only two such cases have been reported in the English literature. We report a third such case in a 4-year-old girl. The recurrence and extensive spread were excellently demonstrated by MRI.

Unattached intracranial extra-axial schwannoma.

We describe an intracranial extra-axial petroclival schwannoma which did not arise from any cranial nerve, nor was it attached to brain parenchyma or dura. The possible pathogenesis is discussed.

Extra-axial clival blastomycosis granuloma: a case report.

A case of extra-axial fungal (Blastomyces dermatitidis) granuloma in the region of the lower clivus is presented. The lesion simulated a meningioma both on radiological examination and on the macroscopic appearance at operation.

Thoracic disk prolapse.

Fifteen patients with thoracic disc prolapse were treated at our institution over a 23 year period. The clinical presentation, investigations, surgical treatment and results of these cases are analysed retrospectively in this report. Lower dorsal region disc prolapse formed the majority of cases. Local and radicular pain, motor weakness, bladder and bowel involvement were the principal presenting features. Five cases had acute presentation while the rest had chronic and progressive symptomatology. All cases were treated by posterior decompressive laminectomy operation and in five discoidectomy was performed. It was observed on long term follow up than patients who underwent discoidectomy faired better than those in whom only laminectomy was performed.

Intraparenchymal schwannoma of the frontal lobe.

A 45 year old woman with bifrontal headaches and progressive diminution in vision over 6 months was found to have bilateral papilloedema. CT scan showed large right frontal lesion with surrounding oedema. Right basal frontotemporal craniotomy was performed to excise the multinodular, intraparenchymatous tumor. Hispathology confirmed the diagnosis of schwannoma. Post-operative course was uneventful with disappearance of pre-operative signs and symptoms.

An unusual trigeminal neurinoma.

We report a large trigeminal neurinoma in an 18-month-old child involving the Gasserian ganglion and all three divisions in a plexiform pattern. The tumour in the ophthalmic division extended all the way to the supraorbital nerve. The child presented with proptosis which had been observed since she was 4 months of age. There was a family history of neurofibromatosis.

Massive benign osteoblastoma of the clivus and atlas.

A case of massive benign osteoblastoma involving the clivus and atlas is reported. Usually, these tumours involve the posterior elements of a vertebra and are detected when small as a result of the usual presenting symptom of pain. The unusual site, massive size and presentation with neurological deficits are rare for benign osteoblastomas. The problems encountered in the surgical management of the patient are discussed.

Dural cavernous haemangioma of posterior cranial fossa.

A rare case of extracerebral dural cavernous angioma sited near the sigmoid sinus is reported. This 60 yr old male patient gave history of episodic ataxia of left sided limbs experienced twice on same day and occasional giddiness. Examination did not reveal any findings. A mass was diagnosed on CT Scan following which angiography was carried out. The features matched with those of a meningioma. Retro-sigmoid craniectomy was performed. Occipital artery was coagulated. Tumor was dissected out. Post-operative course of the patient was uneventful. Histopathology revealed that the mass was a cavernous haemangioma.

Craniopharyngioma: treatment by conservative surgery and radiation therapy.

Benign neoplasms are curable only when excised. This applies even to craniopharyngiomas. The proximity of craniopharyngiomas to the hypothalamus and neurovascular structures makes total excision difficult to achieve. Over the last 3-4 decades, it has become increasingly obvious that craniopharyngiomas respond to radiation therapy. Early, unhappy results with major excisions have prompted us to adopt a policy of conservative surgery and radiation therapy to the residual tumour. Preliminary results suggest a good outcome in 35 of the 63 patients so treated from 1981. Details of the study are presented.

Trans-sphenoidal excision of craniopharyngiomas.

Craniopharyngiomas have been by and large excised by the transcranial route. Since 1982, 11 patients have been operated by the traus-sphensidal route in the department. The clinical features with which they were presented, diagnostic investigations, details of surgical procedures and follow-up analysis is being presented here. A retrospective study of radiological investigation was done to determine the features that help decide the choice of surgical approach to these lesions. Only lesions that were primarily intrasellar, cystic and those that expanded the sella could be treated by the trans-sphenoidal route. Associated suprasellar extensions could also be removed. Predominantly calcified or firm, fleshy tumours lent themselves poorly to removal by the trans-sphenoidal route.

Intracranial ectopic pituitary tumour.

Pituitary tumours originating primarily from sites other than the sella turcica are rare. A case of an ectopic pituitary tumour in the region of the lesser wing of the sphenoid is reported. The patient presented with signs and symptoms of a progressive increase in intracranial pressure. CT scan appearances resembled those of a sphenoid wing meningioma. The vascular lesion was partially excised. Histology showed it to be a pituitary tumour.

Dural sinus and cerebral venous thrombosis.

Eighty patients with 'primary' dural sinus and cerebral venous thrombosis were seen over a period of 16 years. There was an equal distribution amongst the sexes and the largest number of patients presented in the third decade. The commonest predisposing factors were puerperium, pregnancy, synthetic steroid contraceptives and anaemia. Seventy patients presented in an acute fashion with headache, focal or generalized seizures and focal neurological deficits. Ten patients presented in a subacute to chronic manner, with features to suggest an intracerebral space-occupying lesion. The investigation of choice was angiography. Thirty-five patients were treated conservatively with anticonvulsants, low molecular weight dextran and anti-oedema measures. Anti-coagulants were not used for fear of haemorrhage in the associated red infarcts. Antibiotics were not needed as infection played no part in the pathogenesis. Thirty-four patients needed an operation which took the form of a decompressive craniotomy and dural closure with the aid of a pericranial graft. The conservatively treated group appeared to fare better only because it included patients with a milder ictus. Forty patients improved, three remained unchanged and 37 expired. Autopsy in the 35 of the 37 patients showed cortical vein and sinus thrombosis and oedema with a haemorrhagic infarct. Long term follow-up showed good recovery of neurological function, but epilepsy was a troublesome sequel and needs regular anti-epileptic drug treatment.