Cerebral angiitis in four patients with chronic GVHD.

There is growing evidence that GVHD affects the central nervous system (CNS). In this study, we describe the long-term follow-up of four allogeneic BM recipients who developed cerebral angiitis-like disease probably due to GVHD. The patients developed focal neurological signs, cognitive deficits and/or coma in association with GVHD, 2-18 years after transplantation, following reduction of immunosuppressive therapy. Magnetic resonance imaging was variable, showing generalized brain atrophy, ischemic lesions or leukoencephalopathy. Diagnosis of cerebral angiitis was confirmed by histopathological analysis of bioptic brain tissue and response to immunosuppressive therapy. By means of immunohistochemistry and immunofluorescence, perivascular lymphomononuclear cerebral infiltrates were shown to express the adhesion receptor, CD11a, and the chemokine receptor, CCR5. Our findings imply that GVHD should be considered in the differential diagnosis of noninfectious angiitis-like disease of the CNS in long-term survivors after allogeneic BMT. Infiltrating cells, in analogy to typical target organs of GVHD such as skin or liver, expressed CD11a and CCR5. These findings could be of etiopathological, diagnostic and therapeutic relevance.

[The so-called spontaneous low CSF pressure pressure syndrome. Case results indicating a disturbance in CSF/blood volume regulation]. / Das so genannte spontane Liquorunterdrucksyndrom Kasuistische Hinweise auf eine Störung der Liquor-/Blutvolumenregulation.

The new IHS classification describes under the paragraph 7.2.3 the headache attributed to spontaneous low CSF pressure. We report on four patients with such a headache and discuss the probable pathophysiology, including results published in the literature. It seems that not the low CSF pressure itself is the cause for the headache but the unphysiological, increased vasodilatation of intracranial and epidural veins. This dilatation of veins also shows up in the typical radiological findings with meningeal contrast enhancement and enlarged epidural veins. A trial with caffeine, theophylline, or indomethacin is recommended; otherwise, the most effective treatment option is an epidural blood patch, which is effective also in the absence of a documented CSF leak.

Prospective evaluation of neurological complications after allogeneic bone marrow transplantation.

OBJECTIVE: To determine the spectrum and frequency of neurologic sequelae after allogeneic bone marrow transplantation (BMT) and to define a risk profile of the patients. METHODS: A prospective follow-up of 71 allogeneic bone marrow recipients 14 +/- 3 months after transplantation. Patients underwent a neurologic examination, a neuropsychological test battery, and cranial MRI before and after BMT. RESULTS: A large proportion of patients (65%) developed sequelae after BMT. Acute complications of defined etiology occurred in 18% of the patients and led to death in 9% of the study population. A total of 47% of the patients developed new neurologic abnormalities of undefined origin that were mild and subacute and predominantly affected the peripheral nervous system. The cognitive and neuroradiologic outcome was favorable in a majority of these patients, but a small subgroup exhibited cognitive deterioration and white matter lesions. Risk factor analysis identified acute graft-versus-host disease (GvHD) and other variables partly related to GvHD such as long-lasting immunosuppression as the main predictors of sequelae after allogeneic BMT. The authors have established an association with various factors but, owing to the observational character of this study, conclusions about the etiology of the findings are unclear. CONCLUSION: Neurologic complications significantly contribute to the morbidity and mortality of patients receiving allogeneic BMT. Subclinical abnormalities, cognitive deficits, and white matter lesions detected 1 year after BMT in a subgroup of patients may be related to more extensive CNS changes observed after transplantation in an earlier retrospective study and may be associated with the risk factor chronic GvHD/immunosuppression.

[Neuromuscular complications after allogeneic bone marrow transplantation]. / Neuromuskuläre Komplikationen nach allogener Knochenmarktransplantation.

Neuromuscular syndromes following allogeneic bone marrow transplantation (BMT), although occasionally described,were not the focus of studies concerning neurologic complications following bone marrow transplantation. In this study,we summarize different polyneuropathy syndromes following BMT and report on patients with myasthenia gravis and inflammatory neuromuscular disorders such as myositis or fasciitis. Concerning the etiology of neuropathies, a neurotoxicity of immunosuppressants,a preexisting disorder due to the underlying disease as well as an association with graft-versus-host disease (GVHD) is discussed.GVHD-associated polyneuropathies as well as muscular complications have been found to occur during the early BMT phase, while myasthenia gravis is a late neurologic complication of GVHD.

Detection of Mycoplasma pneumoniae DNA in cerebrospinal fluid of a patient with M. pneumoniae infection-"associated" stroke.

A 36-year-old woman presented with an acute ischemic stroke and a concomitant Mycoplasma pneumoniae infection that had been proven clinically, bacteriologically, and serologically. M. pneumoniae DNA was demonstrated in cerebrospinal fluid by positive nested polymerase chain reaction, and intrathecal antibody production was also detected. Contrary to previous reports about M. pneumoniae-associated stroke, most thrombostatic abnormalities in this patient occurred after stroke onset. Although the cause of stroke remains unclear in this patient, central nervous system invasion of M. pneumoniae DNA has to be considered a possible cause in rare cases of cerebral ischemia.

[Parry-Romberg syndrome and Rasmussen syndrome: only an incidental similarity?]. / Parry-Romberg-Syndrom und Rasmussen-Syndrom: nur zufällige Ahnlichkeiten?

The Parry-Romberg syndrome is a rare and poorly understood disease characterized by slowly progressive, localized atrophy of the skin, subcutaneous tissue, muscles, and bones. The atrophy is typically localized in the face and begins in youth. In some patients, imaging can show the lesions and atrophy of the ipsilateral hemisphere of the brain. We report on a patient in whom the disease has lasted 36 years and discuss the possibility that the Parry-Romberg syndrome is related to known autoimmune disorders of the soft tissue (e.g., linear scleroderma) and Rasmussen's syndrome. There are some remarkable clinical similarities between these two syndromes, including age of onset, unilateral manifestation, and occurrence of focal seizures. It is most probable that both diseases have an autoimmunological background.

Cerebral involvement in graft-versus-host disease after murine bone marrow transplantation.

Neurologic manifestation of graft-versus-host disease (GvHD) after allogeneic bone marrow transplantation (BMT) has until now been limited to rare neuromuscular syndromes. Investigating cerebral findings using a murine BMT model, the authors found parenchymal lymphocytic inflammation, microglia activation, and mild cerebral angiitis-like changes in allogeneic transplanted animals but not in syngeneic controls. These findings suggest that cerebral involvement during GvHD may be a new neurologic complication after BMT.

Intracranial dural arteriovenous fistula with spinal medullary venous drainage.

We report on a 46-year-old patient in whom an intracranial dural arteriovenous (AV) fistula, supplied by a branch of the ascending pharyngeal artery, drained into spinal veins and produced rapidly progressive symptoms of myelopathy and brainstem dysfunction including respiratory insufficiency. Magnetic resonance imaging studies demonstrated brainstem oedema and dilated veins of the brainstem and spinal cord. Endovascular embolization of the fistula led to good neurological recovery, although the patient had been paraplegic for 24 h prior to embolization. This case demonstrates the MRI characteristics of an intracranial dural AV fistula with spinal drainage and illustrates the importance of early diagnosis and treatment. Even paraplegia may be reversible, if angiography is performed and the fistula treated before ischaemic and gliotic changes become irreversible.

[Neurological complications after organ transplantation]. / Neurologische Komplikationen nach Organtransplantation.

Following organ transplantation, 30-60% of patients develop neurologic complications which can be classified as pre-existing deficits due to the underlying disease, complications during surgery, metabolic encephalopathies, neurotoxicity of immunosuppressant agents, opportunistic CNS infections, and secondary malignomas as indirect side effects of immunosuppression. While encephalopathies, seizures, or CNS infection can occur in all types of transplantation, some specific neurological complications exist for different types of organ transplantation. In this review, the clinical symptoms and treatment of both the common neurological complications as well as the particular neurological syndromes after liver, heart, and bone marrow transplantation are discussed.

Angiitis of the central nervous system after allogeneic bone marrow transplantation?

BACKGROUND AND PURPOSE: There is only limited information about late neurological complications after bone marrow transplantation (BMT). The purpose of this study is to describe a cerebral angiitis-like syndrome after allogeneic BMT. METHODS: Clinical and diagnostic findings of 5 BMT patients with chronic graft versus host disease and neuropathological data of 1 patient were reported. RESULTS: In the described patients, focal neurological signs and neuropsychological abnormalities occurred years after BMT. MRI revealed periventricular white matter lesions, lacunar or territorial infarctions, leukoencephalopathy, and hemorrhages. Angiitis of the central nervous system was confirmed in 1 patient at autopsy, and an angiitis-like syndrome was suspected in the other patients because of the clinical course and response to treatment. Three patients received cyclophosphamide and steroids (2 improved, 1 died), 1 patient improved after steroids alone, and 1 patient without immunosuppressive therapy deteriorated further. CONCLUSIONS: We propose that an angiitis-like syndrome of the central nervous system can be a neurological manifestation of graft versus host disease, which should be considered a possible cause of cerebral ischemic episodes and pathological MRI scans in BMT patients with graft versus host disease.

Neurological and neuroradiological findings in long-term survivors of allogeneic bone marrow transplantation.

The aim of this study was to assess neurological, neuropsychological, and neuroradiological findings in long-term survivors of allogeneic bone marrow transplantation (BMT) who were recruited from a hematological outpatient clinic. In addition, risk factors for the development of late neurological complications were identified. In contrast to previous studies on autopsied patients, our study design provoked a bias away from increased neurological sequelae, because patients with early complications after BMT were excluded. Fifty-nine allogeneic patients and 7 autologous BMT patients underwent clinical examination, short neuropsychological testing, and cranial magnetic resonance imaging (MRI) 34 +/- 26 months after BMT. The pathological results of the neurological examination (abnormal 64%) and the MRI examination (white matter lesions, 54%; atrophy, 11%) were associated with the occurrence of chronic graft-versus-host disease (GvHD) evolving from acute GvHD, with corticosteroid therapy and with cyclosporine medication. Neuropsychological impairment (cognitive deficits, 37%) was associated with long-term cyclosporine medication and age. No influence of pre-BMT disease, BMT donor status, or the conditioning regimen was found. These results suggest that the frequent neurological abnormalities in long-term survivors of allogeneic BMT are associated with chronic GvHD and with the resulting immunosuppression as major risk factors.

[Antinuclear and anticardiolipin antibodies in primary headache syndromes]. / Antinukleäre- und Anticardiolipinantikörper bei primären Kopfschmerzsyndromen.

UNLABELLED: Some recent studies report on slightly increased serum levels of anticardiolipin IgG antibodies in patients with migraine with and without aura. METHODS: To confirm these results we investigated the frequency of anticardiolipin IgG and IgM antibodies, the anti-nuclear antibodies, and the serum complement in patients with migraine without aura (n=47), migraine with aura (n=10), cluster headache (n=12), and chronic headache of the tension type (n=31) according to the IHS classification and using commercially available tests. RESULTS: Compared with a group of healthy subjects (blood samples were taken during blood donation), the patients with and without migraine had slightly positive anticardiolipin IgG antibodies significantly more often (22.8% to 4.5%). The other headache patients did not exhibit an increased incidence (9.7% and 0%). Compared to the neurological controls (13%) there was a strong tendency towards more often positive titers in the migraine patients. CONCLUSION: Our finding of increased incidence of positive anticardiolipin IgG antibodies in migraine patients (also reported in other studies) raises the question if these antibodies unspecifically support the occurrence of a migraine attack by increasing the interaction of blood cells and the endothelium. Furthermore, we discuss whether the observed increased incidence of strokes in patients with migraine may in part be caused by the also increased incidence of anticardiolipin antibodies, which are an independent risk factor for stroke.

[Herpes zoster: follow-up, complications and therapy]. / Herpes zoster: Verlauf, Komplikationen und Therapie.

In clinical practice herpes zoster infections are common. The cause is the reactivation of the herpes varicella virus that persists in the sensory ganglia after an earlier primary infection with shingles. There are several neurological complications such as meningitis, ventriculitis, encephalitis, myelitis, cerebral angiitis, myositis, paresis of motor nerves, acute polyneuritis, and most commonly post-zoster neuralgia. A proposed reason for these complications is the direct infiltration of the virus or a hematogenous infection. Some of the complications can be treated symptomatically such as post-zoster neuralgia and the occurrence of certain complications that can be prevented by the right choice of acute therapy.

Immunophenotyping of lymphocyte subsets in bronchoalveolar lavage fluid. Comparison of flow cytometric and immunocytochemical techniques.

In order to compare flow cytometry with the conventional peroxidase anti-peroxidase method for the immunophenotyping of bronchoalveolar lavage fluid (BALF) lymphocytes, we studied BALF samples from 27 patients with various interstitial lung diseases. The results achieved with both methods were consistent concerning CD3+ pan T cells, CD4+ T helper/inducer, CD8+ T suppressor/cytotoxic and CD57+ natural killer cells. In contrast, a statistically significant lower anti-HLA-DR positive subset was obtained with flow cytometry than with the immunoperoxidase method (p less than 0.005). Since regression analyses and reliability counts showed further agreement between the methods, we conclude that flow cytometric immunophenotyping of BALF lymphocytes leads to similar, if not better, subset analyses than the immunoperoxidase method.