[Combined immunosuppression with cyclosporin A, mycophenolate mofetil (MMF) and dexamethasone for activity control of recurrent secondary hemophagocytic lymphohistiocytosis (sHLH) with underlying systemic lupus erythematosus (SLE)]. / Kombinierte Immunsuppression mit Cyclosporin A, Mycophenolatmofetil (MMF) und Dexamethason zur Aktivitätskontrolle einer rezidivierten, sekundären hämophagozytischen Lymphohistiozytose (sHLH) auf dem Boden eines systemischen Lupus erythematodes (SLE).

A 42-year-old female patient was admitted to hospital due to acute neurological symptoms (dysarthria, disorientation). After exclusion of cerebral ischemia and hemorrhage an autoimmune encephalitis was diagnosed. Shortly before as an outpatient the suspicion of the presence of systemic lupus erythematosus (SLE) was voiced. The patient showed a constellation of high levels of inflammatory laboratory parameters and within a few days developed a severe pancytopenia. In the presence of all diagnostic criteria a secondary hemophagocytic lymphohistiocytosis (sHLH) was diagnosed and confirmed by a kidney biopsy during the course of the underlying SLE. The immunosuppressive treatment with etoposide and high-dose dexamethasone according to the HLH-94 protocol only showed temporary success. After 3 weeks of treatment with a protocol-conform dose reduction, under running treatment a new exacerbation of symptoms was confirmed. A renewed dose escalation of the drugs used did not lead to control of the symptoms. The inflammatory activity could only be sustainably controlled by the use of cyclosporin A in combination with mycophenolate mofetil (MMF) and dexamethasone. After stabilization of the condition of the patient, an outpatient follow-up care was possible.

Encephalitis with radial perivascular emphasis: Not necessarily associated with GFAP antibodies.

OBJECTIVE: Autoimmune steroid-responsive meningoencephalomyelitis with linear perivascular gadolinium enhancement in brain MRI is regarded as glial fibrillary acidic protein (GFAP) astrocytopathy characterized by anti-GFAP antibodies (ABs). We questioned whether anti-GFAP ABs are necessarily associated with this syndrome. METHODS: Two patients with a strikingly similar disease course suggestive of autoimmune GFAP astrocytopathy are reported. Clinical examination, MRI, laboratory, and CSF analysis were performed. Neuropathologic examination of brain tissue was obtained from one patient. Serum and CSF were additionally tested using mouse brain slices, microglia-astrocyte cocultures, and a GFAP-specific cell-based assay. RESULTS: Both patients presented with subacute influenza-like symptoms and developed severe neurocognitive and neurologic deficits and impaired consciousness. MRIs of both patients revealed radial perivascular gadolinium enhancement extending from the lateral ventricles to the white matter suggestive of autoimmune GFAP astrocytopathy. Both patients responded well to high doses of methylprednisolone. Only one patient had anti-GFAP ABs with a typical staining pattern of astrocytes, whereas serum and CSF of the other patient were negative and showed neither reactivity to brain tissue nor to vital or permeabilized astrocytes. Neuropathologic examination of the anti-GFAP AB-negative patient revealed infiltration of macrophages and T cells around blood vessels and activation of microglia without obvious features of clasmatodendrosis. CONCLUSIONS: The GFAP-AB negative patient had both a striking (para)clinical similarity and an immediate response to immunotherapy. This supports the hypothesis that the clinical spectrum of steroid-responsive meningoencephalomyelitis suggestive of autoimmune GFAP astrocytopathy may be broader and may comprise also seronegative cases.

Multiple sclerosis and the autonomic nervous system.

Symptoms related to alterations of the autonomic nervous system are frequent in patients with multiple sclerosis (MS). Bladder or bowel dysfunction or impairment of sexual performance is highly distressing for most MS patients,whereas the clinical relevance of other autonomic symptoms is less clear. Cardiovascular autonomic alterations might relate to clinical signs such as orthostatic intolerance; a relationship with fatigue is uncertain. However, the frequency of abnormal findings in tests for the cardiovascular autonomic system varies due to the lack of standardized test performance or differentially used cut-off values. The incidence of additional symptoms such as pupillomotor or sweating alterations and especially their relationship to overall autonomic nervous system abnormalities is not well known. Although their impact on daily life is low, they can at least serve as diagnostic tools. Beside these clinical aspects, alterations of the autonomic nervous system have also been reported to alter immunological cascades in experimental conditions. However, corresponding results have not been confirmed in clinical trials yet.

Is there a differential impact of fatigue and physical disability on quality of life in multiple sclerosis?

To investigate the quantitative impact of fatigue on health-related quality of life (HRQoL) in multiple sclerosis (MS) and to determine whether fatigue was related to HRQoL independently from bodily disability, data on HRQoL were ascertained for 87 patients with definite MS by using the SF-36. HRQoL scores and subscores were related to the basic MS disability score (EDSS) and further MS parameters, and to fatigue, which was assessed by using different fatigue scales. Factors related to predominantly physical but not mental HRQoL aspects were identified as related to EDSS, duration of disease, and age. Different fatigue scores did impact significantly on both physical and especially mental HRQoL. The influence of fatigue on physical HRQoL was independent from EDSS. Fatigue experience reduces HRQoL markedly and independently from EDSS. Therefore, fatigue assessment provides additional information to disability-derived scales such as the EDSS with relevant implications for therapeutic decisions.

Mild cognitive impairment after viral meningitis in adults.

OBJECTIVE: To evaluate cognitive outcome in unselected patients with previously diagnosed viral meningitis. METHODS: Twenty-one unselected patients were examined neurologically, psychiatrically, and psychometrically 25+/-12 months after the acute stage of viral meningitis. The results were compared with the results of twenty-one healthy controls. RESULTS: Despite of a very good clinical outcome in the post-meningitis group patients performed significantly worse on tasks concerning non-verbal memory functions (BVRT), attention and speed of cognitive performance (WMS-3) even when there was no sign of parenchymal involvement. Forty percent of the patients were categorised as suffering from mild to moderate cognitive impairment. CONCLUSIONS: Viral meningitis in adults results in mild cognitive impairment in a significant proportion of patients that is not identified by clinical examination or cognitive screening tests. Nevertheless, even mild deficits in non-verbal learning and cognitive speed might lead to overstrain and handicap in complex situations of daily living and working. We therefore recommend that the neuropsychiatric evaluation of all patients with intracranial infections include neuropsychological testing.