Movement disorders in adult patients with classical galactosemia.

Classical galactosemia is an autosomal recessive inborn error of metabolism leading to toxic accumulation of galactose and derived metabolites. It presents with acute systemic complications in the newborn. Galactose restriction resolves these symptoms, but long-term complications, such as premature ovarian failure and neurological problems including motor dysfunction, may occur despite adequate treatment. The objective of the current study was to determine the frequency and phenotype of motor problems in adult patients with classical galactosemia. In this cross-sectional study, adult patients with a biochemically confirmed diagnosis of galactosemia attending our clinic were assessed with an interview and neurological examination and their notes retrospectively reviewed. Patients were classified according to the presence/absence of motor dysfunction on examination. Patients with motor dysfunction were further categorized according to the presence/absence of reported motor symptoms. Forty-seven patients were included. Thirty-one patients showed evidence of motor dysfunction including: tremor (23 patients), dystonia (23 patients), cerebellar signs (6 patients), and pyramidal signs (4 patients). Tremor and dystonia were often combined (16 patients). Thirteen patients reported motor symptoms, with 8 describing progressive worsening. Symptomatic treatment was effective in 4 of 5 patients. Nonmotor neurological features (cognitive, psychiatric, and speech disorders) and premature ovarian failure were more frequent in patients with motor dysfunction. Motor dysfunction is a common complication of classical galactosemia, with tremor and dystonia the most frequent findings. Up to one third of patients report motor symptoms and may benefit from appropriate treatment. Progressive worsening is not uncommon and may suggest ongoing brain damage in a subset of patients.

Atypical parkinsonism and cerebrotendinous xanthomatosis: report of a family with corticobasal syndrome and a literature review.

Cerebrotendinous xanthomatosis is an autosomal recessive inborn error of cholesterol metabolism. It presents with systemic and neurological symptoms, rarely including parkinsonism. Presented here are a clinical description of a new family with cerebrotendinous xanthomatosis and parkinsonism and a review of 13 additional cases reported in the literature. The index case developed corticobasal syndrome, previously not reported in cerebrotendinous xanthomatosis. His brother had parkinsonism with cerebellar features and cognitive impairment. In a literature review, median age of onset of parkinsonism was found to be 40 years. Nearly all patients had other neurological symptoms: cognitive (93%), pyramidal (93%), or cerebellar (53%). All patients had walking difficulties, with falls in 27%. Systemic features were common: cataracts (93%) or tendon xanthomata (87%). Frequent MRI abnormalities included cerebellar atrophy (100%), cerebral atrophy (80%), and dentate nuclei signal changes (80%). Functional dopaminergic imaging often demonstrated presynaptic denervation. Improvement with levodopa was frequent (91%) but mild. Progressive neurological decline occurred in 92% of patients despite treatment with chenodeoxycholic acid. Cerebrotendinous xanthomatosis should be considered in the differential diagnosis of atypical parkinsonism, including corticobasal syndrome, particularly with early age of onset and in the context of a complex neurological phenotype. Tendon xanthomata, early-onset cataracts, and radiological findings of cerebellar atrophy with lesions of the dentate nuclei are useful clinical clues. Symptomatic treatment with levodopa may help, but progressive neurological decline is frequent despite treatment with chenodeoxycholic acid.

An ITPR1 gene deletion causes spinocerebellar ataxia 15/16: a genetic, clinical and radiological description.

The purpose of this study was to characterise a novel family with very slowly progressive pure spinocerebellar ataxia (SCA) caused by a deletion in the inositol 1,4,5-triphosphate receptor 1 (ITPR1) gene on chromosome 3. This is a detailed clinical, genetic, and radiological description of the genotype. Deletions in ITPR1 have been shown to cause SCA15/SCA16 in six families to date. A further Japanese family has been identified with an ITPR1 point mutation. The exact prevalence is as yet unknown, but is probably higher than previously thought. The clinical phenotype of the family is described, and videotaped clinical examinations are presented. Serial brain magnetic resonance imaging studies were carried out on one affected individual, and genetic analysis was performed on several family members. Protein analysis confirmed the ITPR1 deletion. Affected subjects display a remarkably slow, almost pure cerebellar syndrome. Serial magnetic resonance imaging shows moderate cerebellar atrophy with mild inferior parietal and temporal cortical volume loss. Genetic analysis shows a deletion of 346,487 bp in ITPR1 (the second largest ITPR1 deletion reported to date), suggesting SCA15 is due to a loss of ITPR1 function. Western blotting of lymphoblastoid cell line protein confirms reduced ITPR1 protein levels. SCA15 is a slowly or nonprogressive pure cerebellar ataxia, which appears to be caused by a loss of ITPR1 function and a reduction in the translated protein. Patients with nonprogressive or slowly progressive ataxia should be screened for ITPR1 defects.

Imaging of parasitic infections of the central nervous system.

Parasitic infections of the central nervous system (CNS) have increased over the last couple of decades, partly due to a drop in the living conditions of large populations in the world and the AIDS epidemic. Parasitic infections of the CNS are indolent and often life threatening, hence, an early diagnosis is imperative. While brain biopsy and laboratory analysis remain the gold standard for diagnosis, neuroimaging contributes significantly to diagnosis and follow-up. Imaging can demonstrate the extent of infection and complications and possibly, the type of parasitic infection when characteristic features are evident. The disappearance of the parasite or inflammation, gliosis, and/or calcification suggest a therapeutic response. The initial experience of the CT scan has been greatly enhanced by MRI which is currently the imaging modality of choice. This has been due to the greater tissue contrast resolution of MRI and its ability to detect subtle changes in the tissue parenchyma. Advanced techniques such as diffusion-weighted imaging (DWI), perfusion imaging (PI), MR angiography (MRA), and MR spectroscopy (MRS) have been used to improve the sensitivity for characterizing the type, viability, and burden of the parasites and the host tissue response. Additionally, it is possible to demonstrate the complications of the primary infection and those secondary to treatment, in some cases.

Angiography and selective microcatheter embolization of a falcine meningioma supplied by the artery of Davidoff and Schechter. Case report.

Angiographic demonstration of the meningeal branch of the posterior cerebral artery, or the artery of Davidoff and Schechter, is extremely rare. The authors describe a case of successful selective catheterization and embolization of a pathologically enlarged artery of Davidoff and Schechter, permitting successful preoperative devascularization of a large falcine meningioma.

Intracranial metastatic mucinous adenocarcinoma with characteristic features on diffusion-weighted imaging and in vivo magnetic resonance spectroscopy.

Intracranial abscesses and metastases are common lesions that might not be differentiated on routine MRI alone. In vivo proton spectroscopy and diffusion-weighted imaging have been used as complementary investigations for improved tissue characterization. In the present report we illustrate the role of mucin and its contribution to signal characteristics on diffusion-weighted imaging in a metastatic mucinous adenocarcinoma.

Pyruvate: an in vivo marker of cestodal infestation of the human brain on proton MR spectroscopy.

PURPOSE: To study intracranial cestodal cysts using in vivo proton magnetic resonance spectroscopy ((1)H MRS) in an effort to identify metabolite(s) that may help in recognizing the parasitic etiology and, perhaps, viability of such tapeworm cysts. Cestodal infestations of the human central nervous system (CNS)-cysticercosis and hydatidosis-are not rare. Identification of a scolex is considered diagnostic of cysticercosis on imaging. In its absence, however, the features are non-specific. MATERIALS AND METHODS: Three patients with intracranial hydatid cysts and 13 patients with intracranial cysticercal cysts (four intraventricular, seven parenchymal, and two subarachnoid racemose cysts) were studied on a 1.5-T MR system. In vivo (1)H MRS was performed by multivoxel two-dimensional hybrid chemical shift imaging technique (TE = 135 msec). In vitro (1)H NMR and mass spectroscopy (matrix assisted laser desorption/ionization [MALDI]) were performed on excised cysticercal and hydatid cyst fluid. MALDI spectra for pyruvate and succinate were also obtained. RESULTS: Alanine, pyruvate, and acetate were seen in all the three hydatid cysts. Lactate was seen in racemose cysticercal cysts. A large resonance at 2.4 ppm, confirmed as pyruvate at mass spectroscopy, was seen in 13 cestodal cysts. Pyruvate was not seen in one each of racemose, intraventricular, and parenchymal cysticercal cysts. CONCLUSION: Pyruvate is the predominant metabolite in cestodal cysts infesting the human CNS. It may be a marker of parasitic etiology and perhaps that of viability of such intracranial cysts.