First report of Creutzfeldt-Jakob disease occurring in 2 siblings unexplained by PRNP mutation.

Sibling concurrence of pathologically confirmed prion disease has only been reported in association with pathogenic mutation of the prion protein gene (PRNP). Here, we report 2 siblings with classic neuropathologic features of sporadic Creutzfeldt-Jakob disease unexplained by PRNP mutation or known risk factors for iatrogenic transmission of prion infection. Possible explanations include coincidental occurrence, common exposure to an unidentified environmental source of prions, horizontal transmission of disease, or the presence of unknown shared genetic predisposition.

Clinical presentation and pre-mortem diagnosis of variant Creutzfeldt-Jakob disease associated with blood transfusion: a case report.

BACKGROUND: Concerns have been raised that variant Creutzfeldt-Jakob disease (vCJD) might be transmissible by blood transfusion. Two cases of prion infection in a group of known recipients of transfusion from donors who subsequently developed vCJD were identified post-mortem and reported in 2004. Another patient from this at-risk group developed neurological signs and was referred to the National Prion Clinic. METHODS: The patient was admitted for investigation and details of blood transfusion history were obtained from the National Blood Service and Health Protection Agency; after diagnosis of vCJD, the patient was enrolled into the MRC PRION-1 trial. When the patient died, brain and tonsil tissue were obtained at autopsy and assessed for the presence of disease-related PrP by immunoblotting and immunohistochemistry. FINDINGS: A clinical diagnosis of probable vCJD was made; tonsil biopsy was not done. The patient received experimental therapy with quinacrine, but deteriorated and died after a clinical course typical of vCJD. Autopsy confirmed the diagnosis and showed prion infection of the tonsils. INTERPRETATION: This case of transfusion-associated vCJD infection, identified ante-mortem, is the third instance from a group of 23 known recipients who survived at least 5 years after receiving a transfusion from donors who subsequently developed vCJD. The risk to the remaining recipients of such transfusions is probably high, and these patients should be offered specialist follow-up and investigation. Tonsil biopsy will allow early and pre-symptomatic diagnosis in other iatrogenically exposed individuals at high risk, as in those with primary infection with bovine spongiform encephalopathy prions.

Efficacy and Safety of Remacemide versus Carbamazepine in Newly Diagnosed Epilepsy: Comparison by Sequential Analysis.

An international trial comparing remacemide hydrochloride with carbamazepine was undertaken in newly diagnosed epilepsy using a novel double-blind, parallel group, double triangular sequential design. Patients with two or more partial or generalized tonic-clonic seizures in the previous year were randomized to 600 mg daily of remacemide or carbamazepine. Subsequent dosage adjustments were allowed while maintaining the blind. The trial completed 20 months after initiation following the second interim analysis. Efficacy data on 449 patients showed carbamazepine to be significantly more effective than remacemide in preventing seizure recurrence (P = 0.003). Median time to first seizure after titration, the primary endpoint, was 112 days for remacemide and 306 days with carbamazepine. Time to second, third, and fourth seizures after randomization all significantly favored carbamazepine. Remacemide was shown unequivocally to be inferior to carbamazepine in this patient population. This study also establishes carbamazepine as a proven treatment for use in subsequent active control comparative trials.

Imaging cadavers: cold FLAIR and noninvasive brain thermometry using CSF diffusion.

There is increasing interest in imaging cadavers for noninvasive autopsies for research purposes. However, the temperature is well below that of in vivo imaging, and a variety of interesting 'cold brain' effects are observed. At lower temperatures conventional FLAIR sequences no longer produce dark cerebrospinal fluid (CSF); T(1) is reduced from about 4.0 sec in vivo to 1.7 sec at 1 degrees C. The diffusion coefficient (DC) of CSF is much reduced (from 3.1 10(-9) m(2)s(-1) in vivo to 1.1 at 1 degrees C). DC values therefore provide a noninvasive thermometer to measure brain core temperature to within 1.0 degrees C. In three cadavers DC values were 1.1-1.5 10(-9) m(2)s(-1), indicating brain core temperatures of 1-10 degrees C, consistent with external thermocouple measurements. An improved inversion time (TI(0)) can then be found for FLAIR. At 10 degrees C this Cold FLAIR sequence (TI(0) = 1.5 sec) gave black CSF. Expressions for CSF DC and T(1) as a function of temperature were produced. A measurement of CSF DC could be converted directly to temperature and the required TI(0) found. In vitro values of CSF DC were about 1% lower than that of water. Thus, FLAIR imaging can be optimized for cadaveric brains at low and unknown temperatures, thereby improving value for autopsy purposes and facilitating comparisons with in vivo imaging.

Primary orthostatic tremor associated with a persistent cerebrospinal fluid monoclonal IgG band.

Primary orthostatic tremor is of unknown aetiology and is believed to be a distinct entity rather than a subtype of essential tremor. We describe the first patient with a typical phenotype of primary orthostatic tremor who has a persistent isolated monoclonal immunoglobulin G band in the cerebrospinal fluid.

Chorein detection for the diagnosis of chorea-acanthocytosis.

Chorea-acanthocytosis (ChAc) is a severe, neurodegenerative disorder that shares clinical features with Huntington's disease and McLeod syndrome. It is caused by mutations in VPS13A, which encodes a large protein called chorein. Using antichorein antisera, we found expression of chorein in all human cells analyzed. However, chorein expression was absent or noticeably reduced in ChAc patient cells, but not McLeod syndrome and Huntington's disease cells. This suggests that loss of chorein expression is a diagnostic feature of ChAc.