Pharmacokinetics of 5-fluorouracil in patients heterozygous for the IVS14+1G > A mutation in the dihydropyrimidine dehydrogenase gene.

5-Fluorouracil (5FU) and capecitabine are two of the most frequently prescribed chemotherapeutic drugs for the treatment of patients with cancer. Administration of test doses of 5FU to eight patients heterozygous for the IVS14+1G > A mutation and five control patients showed that the AUC and clearance were weak parameters with respect to the identification of patients with a DPD deficiency. However, highly significant differences were observed for the terminal half life of 5FU between DPD patients and controls. Thus, a DPD deficiency could be predicted from 5FU blood concentrations measured after the administration of a test dose of 5FU.

[Selective immunoadsorption in neurologic complications of systemic lupus erythematosus]. / Selektive Immunadsorption bei neurologischen Komplikationen eines systemischen Lupus erythematodes.

Vasculitis of the nervous system is a rare cause of multifocal neurologic symptoms and may involve both the central and peripheral nervous systems. Typical symptoms include headache, encephalopathy with cognitive impairment and psychotic symptoms, epileptic seizures, and peripheral neuropathies. Here we report the case of a 71-year-old female presenting with Raynaud's syndrome and paresthesia of the feet. Several weeks later she was admitted to our hospital with a status epilepticus and complex partial seizures. On admission she had mild aphasia, distal paresis of the arms without sensory deficits, and disorientation with hallucinations. Cerebral MRI revealed small, multifocal infarctions in several arterial territories. Multiple cerebral artery stenoses were detected by ultrasound. Examination of the CSF was unremarkable. Serologic tests for autoimmune disorders detected Ro antibodies compatible with systemic lupus erythematosus or Sjögren's syndrome. A sural nerve biopsy revealed ischemic axonal neuropathy. During administration of i.v. methylprednisolone, the symptom progression stopped but dosages could not be tapered due to severe CNS symptoms (mental decline, disorientation, aphasia, hallucinations). Slow but sustained clinical improvement was achieved by immunoadsorption over 3 weeks followed by a combined high-dose immunosuppressive treatment with cyclophosphamide and prednisolone that paralleled a reduction in anti-Ro titers and normalization of cerebral blood flow velocities as detected by repeated transcranial Doppler sonography. Systemic vasculitis may present with multiple neurologic and psychiatric symptoms due to involvement of the central and peripheral nervous systems. After excluding systemic infection, immunosuppressive therapy should be started early. In our case a combination of high-dose methylprednisolone, immunoadsorption with elimination of Ro antibodies, and cyclophosphamide led to the patient's recovery.

Multiple reversible MR signal changes caused by Epstein-Barr virus encephalitis.

This report presents the imaging findings of an unusual case of Epstein-Barr virus (EBV) encephalitis. A young man presented with a short-lasting history of febrile infection, neuropsychologic deficits, ataxia, and seizures. MR imaging revealed fully reversible signal intensities (T2, diffusion-weighted imaging with a decreased apparent diffusion coefficient) in the splenium of the corpus callosum and both posterior hemispheres. EBV infection must be added to the list of differential diagnoses of (reversible) splenial lesions.

[Bilateral hypoglossal nerve palsy following intubation]. / Bilaterale Hypoglossusparese nach Intubationsnarkose.

Hypoglossal nerve palsy following intubation is a rare complication that can be reversible depending on the extent of nerve damage. A 63-year-old male with a sigma carcinoma was repeatedly intubated orotracheally due to postoperative complications. After the fourth intubation, bilateral, complete hypoglossal nerve palsy with severe dysarthria and swallowing disability was observed. A percutaneous endoscopic gastrostomy tube was inserted for nutrition and to prevent aspiration. Cerebral MRI showed no pathological findings, particularly in the brainstem. Electromyographic studies revealed pathological spontaneous activity of both glossal muscles without any motor unit potential consistent with an axonal lesion of both hypoglossal nerves. Nevertheless, complete clinical and electromyographical recovery occurred within 7 months. The bilateral hypoglossal nerve palsy in our patient was probably due to mechanical alteration during intubation, leading to axonotmesis. Hypoglossal nerve palsy following intubation might have a favourable prognosis as long as continuity of the nerve sheath is maintained.

[Differential diagnosis of solitary neurosarcoidosis]. / Differenzialdiagnose der isolierten Neurosarkoidose.

Sarcoidosis is an inflammatory multisystemic disease characterised by noncaseating epithelioid granulomas. The lung is affected in over 90% of patients. According to clinical criteria, the nervous system is involved in 5-9%. However, in autopsy series this number increases to 25%. Solitary involvement of the nervous system without signs of systemic disease is rare and diagnostically cryptic. Due to the wide variety of neurologic symptoms, definite diagnosis of sarcoidosis is possible only by histopathological proof of noncaseating epithelioid granulomas. We report a 51-year-old woman who presented with chronic basal meningitis and involvement of the peripheral and central nervous system due to solitary neurosarcoidosis. Diagnostic procedures and differential diagnosis are discussed.

[Unusual manifestation of zoster sine herpete as unilateral caudal cranial nerve syndrome]. / Ungewöhnliche Manifestation eines Zoster sine herpete als unilaterales kaudales Hirnnervensyndrom.

Multiple lower cranial nerve palsies are a rare complication following varicella zoster virus (VZV) reactivation, especially if typical herpetic eruptions are lacking. We report a case of a 45-year-old, immunocompetent male with unilateral involvement of the cranial nerves VIII, IX, X, and XI without skin lesions. Cerebrospinal fluid (CSF) studies revealed mononuclear pleocytosis with intrathecal antibody synthesis against VZV, while polymerase chain reaction (PCR) did not detect VZV or HSV (herpes simplex virus). The patient almost completely recovered after aciclovir administration. VZV reactivation without rash (zoster sine herpete) may lead to multiple cranial nerve palsies. PCR is a useful tool to detect VZV-DNA in CSF, but negative results do not exclude a reactivation. In case of multiple cranial nerve palsies of unknown etiology with mononuclear pleocytosis in CSF tumors of the skull base, meningitis tuberculosis, and meningeosis have to be excluded, and antiviral therapy should be discussed.

[Granulomatous vasculitis of the CNS as a complication of herpes zoster ophthalmicus]. / Die granulomatöse Vaskulitis des ZNS als Komplikation des Herpes zoster ophthalmicus (HZO).

A 61-year old man with a history of arterial hypertension suffered a left HZO, and was treated with acyclovir. Three weeks later he suddenly developed moderate left hemiparesis particularly of the leg, severe paresis of the right leg, aphasia and somnolence. Treated with IV acyclovir and high-dose corticosteroids deterioration of the right hemiparesis was apparent. Serological and CSF-studies showed acute varicella-zoster virus infection with intrathecal antibody synthesis (antibody specificity index 2.7). On the third day CT scan revealed infarctions in the territory of both anterior cerebral arteries, at the fifth day additionally left striatocapsular infarction. Selective carotid arteriogram showed bilateral occlusions of anterior cerebral arteries in their proximal segment. With a mean delay of seven weeks granulomatous vasculitis is a rare complication of HZO, leading commonly to ischemic infarctions in the region of the middle cerebral artery. Trigeminovascular connections are the probable pathway of virus-transmission from the trigeminal nerve to ipsilateral branches of the circle of Willis. Because of the presumed pathogenesis immediate therapy with high-dose corticosteroids and acyclovir is justified.