What is microvascular white matter disease


pathological changes in the white matter of the brain, which can occur in a variety of diseases. The cause can be, for example, treatable metabolic disorders such as glutaric aciduria type I, as well as almost all other diffuse damage to the brain, for example hypoxic.

Progressive multifocal leukoencephalopathy (PML) Caused by the JC virus, around 80-85% of all adults have come into contact with the virus, but the virus almost only causes symptoms in people whose immune system is compromised, such as AIDS patients or patients after bone marrow transplants or for immunosuppressive medication, Tysabri (natalizumab) - treatment for MS. It has been assumed up to now that the infection with the JVC virus usually occurs in early childhood and that this remains without symptoms. Only under immunosuppression, as in AIDS, does the disease break out (before AIDS, the disease cases were very rare). This results in demyelination in multiple brain regions, caused by a lytic infection of the oligodendrocytes by the JCV. The destruction of these myelin-producing cells leads to the foci in the brain and ultimately to death. HIV-infected people have a high rate of PML in relation to other patients under immunosuppression, 80% of PML infections occur in the context of an HIV infection. Why this is so is still the subject of research. The hypotheses assume that cellular immunosuppression in HIV / AIDS, damage to the blood-brain barrier in HIV and possibly specific specific molecular mechanisms through which HIV promotes JCV gene expression play a role. Since a number of slow viruses are also suspected to be the cause of the disease in MS, there are also suspicions that the JVC plays a role in the development of MS. What is certain is that understanding this potentially immunosuppressive disease is important for future MS therapies. The diagnosis can be difficult, other AIDS complications can look similar in the magnetic resonance image, toxoplasmosis, AIDS-dementia complex, cryptococcal meningitis, lymphomas, cytomegalovirus, and herpes virus infections of the brain are among the differential diagnoses that are difficult to differentiate. Clinically, there are increasing neurological deficits in PML, mostly monoparesis or hemiparesis, gait disorder, speech disorder, visual disorder, cognitive impairment. Those affected die on average six months after diagnosis. The HAART (Highly Active Anti-HIV Therapy) scheme has improved the treatment prognosis. Half of those affected survive a year under this treatment, and there may even be cures.

As Radiation therapy sequence Atrophy, calcifications, telangiectasias, hyalinosis and fibrosis of small vessels, degeneration of the white matter, focal coagulation necrosis, mineralizing microangiopathy and finally radiation leukoencephalopathy can occur in the brain. In children this is often reversible and shows in an apathy syndrome. In adults, the course is less favorable, but difficult to generalize because of the mostly serious underlying diseases. In combination with methotrexate treatment, particularly unfavorable courses with intellectual defects, the risk of developing dementia and possibly fatal outcomes due to leukoencephalopathy are possible. With PCL, this combination has a 10% risk of leukoencephalopathy and a higher risk of less pronounced cognitive impairment. Patients over 50 years of age have a leukoencephalopathy risk of about 40%. There is no known effective therapy for radiation leukoencephalopathy.

Progressive cerebral calcifications and leukoencephalopathy recessive hereditary disease with cerebral (middle) cysts, retinal vascular abnormalities (telangiectasias and angiomas, vitreoretinal bleeding, secondary retinal detachment and glaucoma), bone changes and haematological abnormalities, slowed growth (also Coats plus syndrome). Repeated intestinal bleeding is also reported in half of those affected with this syndrome. In the foreground are strange asymmetrical and increasing calcifications of the brain (basal ganglia, thalami, and brain stem, but also cortex with fluctuating air of the white matter. The disease process is probably caused by an obliterative angiopathy of the small brain vessels, which then slowly obliterate (occluded This leads to a slowly progressive necrosis followed by the calcifications and cysts. Clinically, para or tetraspasticity and epileptic seizures occur. The very rare disease begins between the ages of 6 months and 14 years. Autosomal recessive that too is hereditary CACH syndrome = Childlike ataxia with diffuse hypomyelination of the CNS Leukoencephalopathy with loss of white brain matter and often fatal in childhood.

Reversible posterior leukoencephalopathy syndrome (PLE). Symptomatic: headache, impaired consciousness, loss of vision and epileptic seizures with posterior, subcortical brain edema. In a series of 36 patients (Arch Neurol. 2008; 65 (2): 205-210) 33 (87%) had epileptic seizures, of which 10 (26%) had a focal onset, 14 (37%) had multiple seizures, and one patient had status epilepticus. 35 (92%) had symptoms of encephalopathy, 15 (39%) had visual symptoms, and 20 (53%) had headache. The regression of symptoms occurred on average after 5.3 days (0-32 days). Of the 36 patients, 5 died. During the 1.8 years of follow-up, none of the affected subjects had recurrent epileptic seizures. Antiepileptic treatment is therefore not particularly useful after PLE, but complications are not uncommon. PLE is usually the result of damage to the central nervous system due to high blood pressure (hypertonic crises), but also other damage mechanisms (hypercalcemia, eclampsia, essential hypertension, kidney diseases, vasculitides, thrombotic-thrombopenic purpura, endocrine diseases such as pheochromocytoma, hyperaldosteronism, Cushing's syndrome, porphyria, ingestion of Cocaine, amphetamines, caffeine, immunosuppressants such as cyclosporine A, tacrolimus, immunomodulators such as immunoglobulins, interferon A, interleukin, erythropoietin, cytostatics such as vincristine, cytarabine, cisplatin, cyclosporine), reversible if the cause is treated early. The term â € œreversible posterior leukoencephalopathyâ € is misleading to the extent that this syndrome can also occur in the anterior brain regions and is not limited to the posterior vascular system or the posterior part of the brain. It's not limited to white matter either. In the above-mentioned series of 36 patients, the anterior hemisphere was involved in 22 episodes (58%), gray matter lesions showed 16 (42%), unilateral lesions 2 (5%), in 22 ( 58%) who also affects the brain stem and / or the cerebellum. Bleeding occurred in 2 (5%), recurrence occurred in 2 (5%), and residual MRI changes were seen in 10 (26%). The changes are not completely reversed in all cases. This also applies if the bad is completely receded. The prognosis depends on whether the diagnosis is considered early, especially if the location of the lesions appears atypical. The transition to an irreversible cytotoxic acid can be prevented by initiating consistent therapy. Depending on the cause, treatment consists either in lowering blood pressure or in discontinuing the responsible medication. The aim is to achieve a diastolic blood pressure below 100 mmHg, and the mean arterial pressure to be reduced by 20-25 mmHg within 1–2 hours. In the case of epileptic seizures, anticonvulsant medication is recommended until the MRI changes have completely regressed. Long-term therapy is not considered necessary. Immunosuppressive or cytotoxic drugs should be reduced in dose, if possible even completely discontinued. If you have eclampsia, you should give birth as soon as possible. Regarding the inherited from a defective gene on chromosome 19 p.13.1

CADASIL- Disease (cerebral autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy = Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy) see there. Leukoencephalopathies can also occur during treatment with other cytostatic drugs. An example is the treatment of severe recurrent aphthous ulcers, melanomas or hepatitis C with levamisole or the treatment of colon cancer with levamisole and 5-fluorouracil. The multifocal leukoencephalopathies that then occur are partially reversible when the substances are discontinued. It is important to distinguish it from other white matter damage such as MS. Confluent or spotty damage to the white matter (or white spots in magnetic resonance) otherwise occur in senile leukoencephalopathy (leukoaraiosis), leukodystrophies with myelination anomalies, adrenoleucodystrophy, globoid cell dystrophy, hemodynamic anemia, hemodynamic disorder , arteriovenous malformations, cerebral amyloid angiopathies, sinus vein thrombosis, polychemia, cerebral edema, after stroke, trauma, metastases, obstructive or normal pressure hydrocephalus, after radiation therapy, after intrathecal methotrexate treatment, with encephalitis, temporal arteries, systemic arteries Neurosarcoidosis, multiple sclerosis, M. Alzheimer, M. Binswanger, Creutzfeldt-Jakob disease, hepatic coma, uremia, hypoglycemia, gangliosidoses, mucopolysaccharidoses (Neuroradiology (2007) 49: 1â € “22)

Sources / literature:

K. Khalili, M.K. White, F. Lublin, et al., Reactivation of JC virus and development of PML in patients with multiple sclerosis NEUROLOGY 2007; 68: 985-990 Togni M, Müller NJ, Sartoretti S, Maggiorini M, Krause M: Reversible posterior leukoencephalopathy : Significance in everyday clinical practice. Switzerland Med Wochenschr 1997; 127: 1242â € “1246 Eduardo Canalejo Castrillero, Intracranial hematoma in a patient with AIDS CMAJ â € ¢ May 10, 2005; 172 (10). doi: 10.1503 / cmaj.045090.Progressive Multifocal Leukoencephalopathy (PML) - Progressive Multifocal Leukoencephalopathy as an Initial Manifestation of AIDS -T. Linnankivi, et al., Cerebroretinal microangiopathy with calcifications and cysts NEUROLOGY 2006; 67: 1â € “1 CACH syndrome, Swantje Beyer, et al., Parieto-temporal insult? Switzerland Med Forum 2004; 4: 85-88
H.M. Liu, W.J. Hsieh, C.C. Yang, V.C. Wu, and K.D. Wu, Leukoencephalopathy induced by levamisole alone for the treatment of recurrent aphthous ulcers, NEUROLOGY 2006; 67: 1065â € “1067 S. Herberger et al.,  € œReversible posteriores leukoencephalopathy syndromeâ € neurologist 2006 â € 77: 1218â €“ 1222