Novel KRIT1 mutation and no molecular evidence of anticipation in a family with cerebral and spinal cavernous malformations.

BACKGROUND: Cerebral cavernous malformations (CCM) are vascular brain anomalies which can result in a variety of neurological symptoms. Familial CCM is inherited as an autosomal-dominant trait. There is one study in the literature which reports statistical evidence for anticipation in familial CCM. METHODS: We reevaluated the clinical course of the disease and performed molecular analyses in a previously described three-generation CCM family with apparent anticipation. RESULTS: Disease started at a younger age in each generation, strongly suggesting anticipation. The patient in generation I showed no clinical symptoms by the age of 68, whereas his son became wheelchair-bound at the age of 43 due to an intramedullary cavernous malformation at the thoracolumbar transition of the spinal cord. The patient in generation III had a pons hemorrhage at the age of 11 due to a large brainstem cavernoma. The hemorrhage caused facial palsy and hemiparesis, persisting as Millard-Gubler syndrome. Sequencing of KRIT1 identified a novel frameshift mutation in exon 15 (c.1561delC or p.Leu551X) which cosegregated with the phenotype. Flow-FISH analysis of granulocyte and lymphocyte telomere length showed that telomeres were longest in the youngest affected family member. CONCLUSIONS: We could not find any evidence for either of the two currently known molecular mechanisms for genetic anticipation (i.e., expansion of repetitive DNA elements or progressive telomere shortening) in this family. However, the family presented here raises the important question whether surveillance of CCM families with gradient-echo MRI should not only include the cerebrum, but the spinal cord as well.

Rapid geographical clustering of wound botulism in Germany after subcutaneous and intramuscular injection of heroin.

BACKGROUND: Wound infections due to Clostridium botulinum in Germany are rare and occur predominantly in heroin injectors, especially after subcutaneous or intramuscular injection of heroin ("skin popping"), which is contaminated with spores of C. botulinum. We report a rapid geographical clustering of cases in Germany in a region between Cologne, Bonn, and Aachen with wound botulism and consecutive systemic C. botulinum intoxication in intravenous drug users (IDUs) within 6 weeks in October and November 2005. PATIENTS: A group of 12 IDUs with wound botulism after "skin popping." RESULTS: Clinical data were available in 11 (92%) of 12 patients; in 7 (58%) of the 12 cases, there was cranial nerve involvement including mydriasis, diplopia, dysarthria, and dysphagia, followed by progressing symmetric and flaccid paralysis of proximal muscles of the neck, arms, trunk, and respiratory muscles. Mechanical respiratory support was necessary. Five of the IDUs were treated with antitoxin, but mechanical respiratory support could not be avoided. The mean ventilation duration was 27.4 days (range 6-77 days). In 4 patients (33%), mechanical ventilation could be avoided; two were treated with antitoxin. CONCLUSIONS: This report describes rapid geographical clustering of wound botulism with severe respiratory complications in IDUs after "skin popping," which has not previously been reported either in Germany or any other European country. Based on these observations and those in other European countries, we conclude that there is a trend towards "skin popping," suggesting a change in injection practices in IDUs. Secondly, we conclude that the total number of cases with wound botulism is likely to increase because "skin popping" is the main risk factor.

[Atypical headache and facial pain as a result of hypertrophic pachymeningitis in C-ANCA-positive Wegener's granulomatosis]. / Atypischer Kopf- und Gesichtsschmerz infolge hypertropher Pachymeningitis bei c-ANCA positivem Morbus Wegener.

BACKGROUND: Wegener's granulomatosis (WG) is a systemic vasculitis involving the nervous system in 20-54% of cases; lesions of peripheral nerves are commonest, while manifestation in the central nervous system (CNS) is rarer. Focal hypertrophic pachymeningitis is a very rare complication of WG. This inflammatory thickening and fibrosis of the dura mater is always associated with headaches, whereas cranial nerve lesions, cerebellar symptoms or epileptic seizures occur more rarely. CASE REPORT: A 67-year-old patient, in whom WG had been diagnosed 2 years earlier and who had been treated with immunosuppressants since then, complained of continuous severe, mainly left-sided headache and facial pain for weeks. Cranial MRI showed thickening of the left tentorium cerebelli with obvious contrast enhancement and led to the diagnosis of hypertrophic pachymeningitis. The inflammatory parameters and the C-ANCA (antineutrophil cytoplasmic antibodies) in the serum were raised and CANCA were detectable in the cerebrospinal fluid. The headaches subsided with several days of intravenous high-dose corticosteroids and a simultaneous increase in the immunosuppressive basic medication. On a follow-up MRI after 3 months, the magnetic resonance changes were less apparent, i. e., the hypertrophic pachymeningitis was resolving; C-ANCA were now no longer detectable in the cerebrospinal fluid. CONCLUSION: With newly occurring, unusually severe and persistent headaches in the presence of WG, the very rare complication of hypertrophic pachymeningitis should be considered.

[Multiple cerebral cavernous malformations: typical pattern on MR imaging and appearence of a new lesion in the follow-up MRI]. / Multiple zerebrale kavernöse Angiome --Klassischer MRT-Befund mit Nachweis einer de-novo Gefässmalformation im Verlauf.

Cerebral cavernous malformations (CCM) are common, mostly benign vascular anomalies of the CNS. Clinical features are seizures, headache and focal neurological signs. Often they are asymptomatic. Apart from sporadically cases CCM occur as an autosomal dominant condition. Familial cases are associated with a high frequency of multiple lesions. MRI is most sensitive in the detection of cavernous malformations. The MRI findings of CCM are variable, depending on hemorrhage and calcifications. The typical appearence of CCM are heterogenous "popcorn-like" lesions of different size with a mixed signal core and a hypointense hemosiderin rim. Our report concerns a 22 year old man with multiple cerebral cavernous malformations whose follow-up MRI of brain showed the appearence of a new lesion.