Demyelination in rheumatic diseases

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS) characterised by multifocal areas of demyelination in the white matter of the brain and spinal cord. Autoantibodies, for example antinuclear antibodies, can also be present. MS and other demyelinating processes, such as transverse myelitis and optic neuritis (which may be clinically isolated cases or be part of the clinical spectrum of MS), are sometimes difficult to differentiate from CNS involvement in systemic autoimmune diseases like systemic lupus erythematosus (SLE), antiphospholipid syndrome (APS), Sjoegren's syndrome (SS), and Adamantiades-Behcet disease (BD). An acute isolated neurological syndrome presents the biggest diagnostic problem, since it is common in MS, but can also be the only feature or first manifestation in SLE, APS, SS, and BD. Indeed, the clinical presentation and lesions evidenced by magnetic resonance imaging may be similar.     

Inflammatory cerebro-vascular disease: angiographic findings and distribution patterns (author's transl)]

Although cerebral angiography should be approached with caution in the diagnosis of inflammatory cerebro-vascular disease there are some characteristic angiographic findings which may be helpful for classification and differential diagnosis. The proximal cerebral arteries are favourably affected by basal meningitis and thrombangiitis obliterans with resulting stenoses and occlusions. Whereas those inflammations originating from neighbouring skull structures mostly involve the intracavernous parts of the carotid artery, the tuberculous and mycotic arteritis prefer the supraclinoid carotid siphon. Peripheral vascular changes are found in luetic endangiitis, necrotizing and toxic angiitis and in collagenoses. Simultaneous involvement of the temporal arteries is of great diagnostic importance demonstrating the systemic character of the inflammatory process; in Horton's arteritis it can be a pathognomonic finding. Infectious endocarditis, some mycoses and malaria may lead to embolic occlusion of cerebral vessels. Mycotic aneurysms mostly have a broad base or a fusiform shape and do not prefer the localizations of congenital aneurysms. Angiographically, abscesses, tuberculomas and viral encephalitis may result in circumscribed hypervascularized areas. The characteristic angiographic findings are exemplified and discussed on the basis of 8 cases of inflammatory cerebro-vascular disease (tuberculosis, pneumococcal and unspecific bacterial meningitis, syphilis, mycosis, Takayasu-syndrome, panarteritis nodosa, temporal arteritis).     

Creutzfeldt-Jakob disease and other human transmissible spongiform encephalopathies. Part II

The second part of this work presents the neuropathological problems of the Creutzfeldt-Jakob disease and basic informations about other human prion diseases. General problems of prion diseases and clinical symptoms of Creutzfeldt-Jakob disease were presented in the first part. Prion diseases are also known as transmissible cerebral amyloidoses (TCA) or transmissible (subacute) spongiform encephalopathies (TSE, SSE). There are following human TSE's: Creutzfeldt-Jakob disease (CJD)--the most frequent TSE, and its new variant (vCJD)--a result of BSE's transmission into human, sometimes treated as a separate disease; also: Gerstmann-Str?ussler-Scheinker syndrome (GSS) that may be a variant of familial CJD, kuru--probably a result of sporadic CJD's transmission by cannibalism, and fatal familial insomnia (FFI). Their clinical symptoms (and especially of the CJD), are nonspecific and sometimes variable. The imaging, EEG and other laboratory tests are not specific either. Neuropathological studies are needed but their interpretation may be equivocal. TSE's are characterised by the neurodegenerative process with characteristic spongiosis. However, vacuolisation--similar as in TSE-spongiosis--may occur in some CNS's disorders and in the case of putrescent brain tissue. In some cases of CJD, particularly those of long duration, the neuronal loss and astrocyte proliferation can mask the presence of spongiform changes, especially when vacuoles are not numerous. The only certain diagnostic marker for TSE is PrP(Sc), prion protein, presently believed to be a direct cause for all TSEs (TCAs). The PrP(Sc) has a dominant beta-sheet amyloid structure which makes its detection by immunohistochemical procedure possible only with special pretreatment, e.c.: hydrolytic autoclaving, hydrated autoclaving, incubations: formic acid (or guanidine thiocyanate) pretreatment, also combined pretreatments. These methods are standard diagnostic procedures for transmissible cerebral amyloidoses.     

Neurosarcoidosis: diagnosis and therapy

Sarcoidosis is an inflammatory systemic disease with a prevalence of 20 to 50 of 100,000 inhabitants in West-Germany. Caused by an abnormal immune response to a hypothetic inhalative antigen, a granulomatous inflammation in mediastinal lymph nodes occurs, which frequently extends to the lung and sometimes to other tissues. The nervous system is clinically involved in 5% of the cases. The most frequent neurologic symptom is solitary or combined cranial nerve involvement. Cerebral manifestations are nodular or diffuse granulomatous infiltration of the brain and lymphocytic inflammation of the basal meninges. The rarer myelopathies and peripheral neuropathies often cause major neurological deficits. Muscular involvement, which is present in about half of the cases of sarcoidosis, normally causes clinically silent lesions. Chronic sarcoid myopathy or acute polymyositis are rare. Elements of the diagnostic procedure are X-ray of the lung, measurement of serum Angiotensin-Converting Enzyme (ACE)- and serum Lysozyme (LZM)-levels, Bronchoalveolar lavage, Gallium-67-scanning and Kveim-test. The diagnostic value of these investigations and the typical findings in CSF examination, computed tomography, nuclear magnetic resonance, myelography and electrophysiological investigation are presented. Suspected diagnosis of sarcoidosis should be confirmed by biopsy of non-caseating granulomatous lesions in involved tissues. An initially high dosage corticosteroid therapy for many months to several years is often effective. If this is not helpful in cerebral sarcoidosis whole brain irradiation with 1500 to 3000 rd administered in 10 single doses is indicated. Peripheral neuropathy refractory to therapy with orally administered cortisone should be treated with parenteral ultrahigh steroid therapy.     

Non-MS autoimmune demyelination

Connective tissue diseases can be characterised by central nervous system (CNS) involvement, in some patients manifested by demyelination areas in the white matter of the brain and spinal cord, which are difficult to differentiate from multiple sclerosis (MS) and other demyelinating processes, such as transverse myelitis and optic neuritis. Demyelinating process may be the feature of nervous impairment in systemic lupus erythematosus, Behcet's disease (BD), Sjoegren's syndrome (SS), systemic sclerosis (SSc) or very rarely other systemic autoimmune diseases. An acute isolated neurological syndrome, as the most common symptom of MS can sometimes be the only feature or even first manifestation of nervous impairment in connective tissue disease, hence presenting the diagnostic problem. Although the white matter abnormalities seen by magnetic resonance imaging may be similar in non-MS autoimmune demyelination and MS, it is the most important diagnostic tool in the differential diagnosis of the mentioned conditions. Investigating the presence of various autoantibodies potentially involved in the pathogenesis of demyelinating lesions as well as cerebrospinal fluid (CSF) analysis can be helpful.     

Multiple non-neoplastic lesions in computerized cranial tomography

Multiple intracranial lesions observed in the computerized tomography ever cause worry due to the possibility of neoplastic etiology, although granulomatous diseases (parasitic or not) and vascular diseases can produce this type of lesions. Five patients with clinical picture that suggested expansive intracranial masses and that had multiple lesions in the computerized tomography that suggested neoplastic diseases are presented. In all patients the clinical evolution and/or other complementary diagnostic tests showed the non neoplastic etiology of the lesions. In three patients the lesions were due to parasitic diseases (intracranial tuberculomas in one case and neurocysticercosis in two cases) and in the other two cases the lesions were due to vascular disturbs (cerebral infarcts). The knowledge of the several diseases that can cause multiple intracranial lesions as seen in the computerized tomography allows to direct the etiologic diagnostic that is essential to introduce the correct treatment avoiding irradiation of non neoplastic lesions and unnecessary surgical procedures. In our country, granulomatous parasitic diseases, mainly neurocysticercosis, tuberculosis and fungal diseases must be considered in the differential diagnosis of multiple intracranial lesions observed in the computerized tomography, together with cerebral infarcts and neoplasms.     

Sneddon's syndrome. Case report and literature review

Diagnostic and therapeutic problems of Sneddon's syndrome are reviewed on the basis of the observation of a pregnant 36-year-old female. She had had Hodgkin's disease stage I, curatively treated when she was 23 years old. She developed cerebral ischemic events, initially ascribed to isolated cerebral angiitis, associated with progressive dermatological lesions (generalised livedo racemosa). A temporal artery biopsy did not reveal giant cell angiitis, while the cutaneous arterioles in a biopsy showed marked intimal proliferation without inflammatory cell infiltration. The literature on Sneddon's syndrome is reviewed.     

Cerebral angiitis mimicking posterior leukoencephalopathy

Posterior leukoencephalopathy typically denotes neurotoxicity from immunosuppressive agents, malignant hypertension or eclampsia. It has not been documented in central nervous system angiitis. We present three cases associated with isolated cerebral angiitis after review of all cases of isolated CNS angiitis from 1998 to 2000. Additional lesions beyond the posterior occipital lesions became evident in two cases. A cerebral angiogram and possibly brain biopsy to detect isolated angiitis should be considered in patients with posterior leukoencephalopathy of unknown etiology. Received: 17 June 2002, Received in revised form: 7 November 2002, Accepted: 11 November 2002 Correspondence to E. F. M. Wijdicks, M. D.     

Primary angiitis of the central nervous system: report of five biopsy-confirmed cases from Colombia

INTRODUCTION: Primary (isolated) angiitis of the central nervous system (PACNS) is a rare cause of cerebrovascular disease (CVD), and few leptomeningeal and brain biopsy (LBB)-confirmed cases have been reported from South America. METHODS: We retrospectively reviewed charts of patients with diagnosis of cerebral angiitis admitted between March 1991 and July 2001 to a single university hospital in Medellin, Colombia. Patients with definitive diagnosis of PACNS by Alrawi et al.'s LBB criteria were selected. We excluded other causes of cerebral angiitis as well as cases without LBB confirmation. RESULTS: We report five patients, four men and one woman, with a mean age at onset of 24.4 years, and an average disease progression of 12.4 days. Four presented with headache and motor weakness, three had seizures, and two had alterations of consciousness. Cerebral MRI was abnormal in all five cases; brain CT in four, and cerebral angiography in two. The cerebrospinal fluid (CSF) was abnormal in two patients. Leptomeningeal and brain biopsies revealed mononuclear infiltration in the wall of small blood vessels in all. Three had concurrent meningeal and cerebral involvement, two had necrotizing angiitis, and one had vascular and encephalitic lesions. All received only steroid treatment; the 1-year follow-up revealed good prognosis without relapses. CONCLUSION: We report five biopsy-proven cases of PACNS from Colombia associated with neurological and neuroimaging abnormalities; these patients presented a mild inflammatory disease that was correlated with few CSF abnormalities and good response to single steroid treatment without relapses. Leptomeningeal and brain biopsy is mandatory for a definitive diagnosis.     

Non-specific angiitis and the central nervous system

Central nervous system manifestations of systemic lupus erythematosus are reported in 25 to 60 p. cent of cases and include mental disturbances, epilepsy, focal deficits, and headache. Cerebrospinal fluid (CSF) changes are inconstantly observed. Cerebral scintigraphy may be useful. CT Scan imaging shows infarcts, hemorrhages, or cortical atrophy. Cerebral angiography is usually normal. Pathological examination shows frequent arteriolar lesions in the CNS but their appearance is rarely that of an angiitis. The mechanism of the CNS lesion involves both angiitis and antineuronal antibodies. Diagnosis is difficult when presenting signs are those of CNS involvement, particularly as the ESR can be normal. Serum complement and anti-DNA antibody levels are frequently normal when there is an isolated CNS involvement. Overall prognosis is poor in cases with CNS lesions. The use of corticoids is discussed. Cerebral angiitis is an exceptional finding during the course of rheumatoid arthritis and scleroderma. Central neurological manifestations of Sharp's and Gougerot-Sj?gren's syndromes have recently been reported. CNS lesions are reported in 10 to 20 p. cent of patients with panarteritis nodosa and include mental disorders and disturbance of vigilance, epilepsy, focal deficits, meningeal signs and headache. The CSF is often normal. The CT scan provides images of infarcts, hemorrhages or cortical atrophy. Cerebral angiography may show segmental stenoses and distal occlusions. Pathological examination of the CNS shows mainly lesions in the intracerebral and leptomeningeal arterioles and small caliber arteries. Treatment is by corticoids and immunosuppressors. Angiitis of the CNS is rare and of late onset in Wegener's granulomatosis. Hypersensitivity angiitis rarely affects the CNS, those cases where it is involved being of poor prognosis and probably related to panarteritis nodosa. CNS manifestations in giant cell arteritis and Takayasu's arteritis result from neck artery lesions. The CNS is affected in 20 p. cent of cases in Behcet's disease with resulting isolated aseptic meningitis or a meningo-encephalomyelitis, and intracranial hypertension. The CSF is nearly always abnormal. Cerebral angiography should be directed towards the search for cerebral thrombophlebitis. Pathologically lesions predominate in the brain stem. Meningeal lesions are almost constantly present. Neurological involvement is of poor prognosis, and early corticotherapy must be instituted. The nosological autonomy of Buerger's thromboangiitis obliterans is questioned. Lymphomatoid granulomatosis is a particular type of angiitis in which malignant cell infiltration occurs. The CNS is affected in 20 p. cent of cases, and whatever the treatment the prognosis is poor. Granulomatous angiitis of the CNS has the distinctive feature of lesions affecting the CNS vessels either exclusively or predominantly. The antemortem diagnosis is based on biopsy of the leptomeninges, and treatment with corticoids and immunosuppressors may prove effective.     

Ten year clinical experience with stroke and cerebral vasculitis

Angiitis of the central nervous system (CNS) is difficult to diagnose but potentially fatal. When stroke occurs in a younger individual or is associated with multiple infarcts on imaging, clinicians must decide how far to pursue a possible diagnosis of vasculitis. The aim of this study is to establish the prevalence of primary and secondary cerebral angiitis among patients presenting with stroke. Hospital attendances over a 10 year period were surveyed by searching for diagnostic codes and key words specific for cerebral vasculitis/angiitis. Case notes were reviewed by the authors using two sets of criteria for angiitis of the CNS. Thirty-two patients were initially considered likely to have cerebral angiitis by treating physicians. Thirteen had been admitted to hospital with stroke. During this period, there were 7475 admissions for ischaemic and haemorrhagic stroke. Six patients had a final diagnosis of vasculitic stroke but only one had definite CNS angiitis with a first presentation as ischaemic stroke (0.02%). Most patients who did have cerebral vasculitis developed multifocal or subacute neurological deficits, or already had an immunological disorder known to be associated with secondary CNS angiitis. Of 19 patients given an alternative final diagnosis, the most common were atherosclerotic/embolic cerebrovascular disease (n = 9) and reversible cerebral vasoconstriction syndrome (n = 7). Stroke is rarely the first manifestation of cerebral vasculitis. Our findings suggest that routine screening for angiitis in stroke patients may not be warranted.     

Follow-up examinations by transcranial Doppler ultrasound in primary angiitis of the central nervous system

BACKGROUND: Primary angiitis of the central nervous system (PACNS) is a rare disease. The definite diagnosis is made upon proof of mononuclear inflammation of the vessel wall on brain biopsy. The diagnosis can also be established on clinical grounds, typical findings on intra-arterial angiography and other investigatory grounds excluding other diseases. Therapy comprises an aggressive immunosuppressive approach. Close monitoring of the patients is mandatory. Transcranial Doppler ultrasound (TCD) has not yet been used to follow up the vasculitic lesions in PACNS. CASE: We report on a 32-year-old female with massive cerebral infarctions secondary to multiple large-vessel stenoses because of probable PACNS. The patient was followed closely by means of TCD. During therapy the cerebral blood flow velocities normalized as displayed by TCD. Clinical improvement followed several days after normalization of cerebral blood flow. CONCLUSIONS: TCD is a valuable noninvasive bedside tool to monitor cerebral blood flow velocities and therapy response in patients with cerebral vasculitis, if large arteries are involved.     

Acute subdural effusion in vasculitis

We report a 29-year-old man with a unique presentation of vasculitis as acute unilateral subdural effusion and meningoencephalitis. Magnetic resonance imaging showed a brainstem lesion that spread to the thalamus over time. There were no systemic features of vasculitis other than a positive pathergy test. Histopathological examination from the pathergy site showed neutrophilic infiltrate and leucocytoclastic vasculitis. The condition was steroid responsive and he remained in remission at two years' follow-up. The anatomy of the brainstem lesion, absence of other inflammatory and infective conditions on evaluation suggests a vasculitic pathology either as primary central nervous system angiitis or as neurological presentation of systemic vasculitis like Behetaet's disease although the international diagnostic criteria for Behetaet's were not fulfilled.     

Cerebral venous thrombosis--clinical aspects and consequences

The clinical picture of cerebral venous thrombosis (CVT) depends on the site of thrombosis in the venous system including superficial veins, deep veins and venous sinuses. Thrombotic changes may occur simultaneously in various parts of the venous system. Since CVT may have various causes, the knowledge of its etiology helps to make the diagnosis. In systemic diseases multiple intravascular clots may result, while in localized pathological conditions thrombosis maybe restricted to the lesion site. The clinical picture is often serious, leading to death, or to severe complications such as pulmonary embolism, and to distant complications--like epilepsy or intracranial hypertension being the cause of chronic headaches (lumbar puncture and CSF pressure measurement are helpful in the diagnosis of intracranial hypertension). In order to prevent complications of crucial importance is not only the proper diagnosis (with MRI and venography as the diagnostic techniques of choice), but also an early and prolonged treatment with anticoagulants. Heparin or fractionated heparin is recommended even though there is a possibility of cerebral haemorrhagic lesions.     

Diffusion-weighted MR findings in isolated angiitis of the central nervous system (IACNS)

OBJECTIVES: To describe the diffusion-weighted MR (DWI) findings of isolated angiitis of the central nervous system (IACNS) and narrow the differential diagnosis. METHODS: The DWI findings of two IACNS patients. Apparent diffusion coefficient (ADC) values were measured in the abnormal lesions, and DWI and T2-weighted MR images were visually inspected. RESULTS: IACNS was diagnosed based on clinical history, MR findings and cerebral angiographic findings. DWI showed hyperintense lesions with heterogeneous ADC values (287-1359 x 10(-6) mm2/s), which indicate the coexistence of cytotoxic and vasogenic oedema. CONCLUSIONS: The findings suggest that the various stages of inflammatory process with ischaemia might exist in IACNS and allow a differentiation from the usual arterial ischaemic infarction. DWI with ADC map can be a useful non-invasive diagnostic test increasing specificity in the diagnosis of IACNS, combined with conventional MRI and cerebral angiography.     

Isolated angiitis of the central nervous system: a case presented with atypical psychiatric symptoms

Isolated angiitis of the central nervous system (IACNS) is a rare form of angiitis limited to the central nervous system. The clinical finding of the combined series revealed that headache was the most common symptom within a combination of focal and diffuse neurological deficits. The case, a 28-year-old man, is presented; the clinical presentation and diagnostic difficulties are discussed. The patient's symptoms began with an obvious atypical depression. In spite of an antidepressive treatment, his symptoms continued to worsen with personality, mood changes and euphoria added to the clinical picture. Meanwhile after several transient ischemic attacks, 6 months later, he was admitted with neurological symptoms including headache, diplopia, and cerebellar ataxia. The radiological investigation was mimicked by primary brain lymphoma. The brain biopsy excluding of lymphoma revealed parenchymal hemorrhage with nonspecific degenerative changes. In systemic investigation, no underlying cause for vasculitis could be found. Neurological but not psychological deficits and radiological lesions of the patient improved with steroid therapy. Since we could not find features of systemic vasculitis, the patient's lesions responded to corticosteroid treatment and neuropathological investigation revealed no lymphoma, We concluded that the most probable diagnosis would be IACNS.     

Herpes zoster ophthalmicus and delayed contralateral hemiparesis caused by cerebral angiitis: Diagnosis and management approaches

Four patients with herpes zoster ophthalmicus and delayed contralateral hemiparesis are described, and their findings are compared with those in patients previously reported in the English language literature. The current patients evidenced multifocal ipsilateral cerebral angiitis by angiography and multifocal infarcts in the distribution of the ipsilateral middle cerebral artery by computed tomographic scanning. Cerebrospinal fluid showed mononuclear pleocytosis, positive oligoclonal bands, and an elevated immunoglobulin G index. Two patients were treated with corticosteroids and acyclovir, and 1 with corticosteroids alone, all without apparent response. Necrotizing angiitis ipsilateral to the herpes zoster ophthalmicus was demonstrated postmortem in 1 patient with multifocal cerebral infarction and progressive leukoencephalopathy. Neither herpes varicella zoster immunocytochemical reactivity nor viral inclusions were seen. The leukoencephalopathy associated with herpes varicella zoster either may be caused by cerebral angiitis or, as previously reported, may be a temporally remote manifestation of persistent herpes varicella zoster infection. The cerebral angiitis associated with herpes varicella zoster is histologically similar to granulomatous angiitis, and both may be related to herpes varicella zoster infection of the cerebral vasculature.     

Primary angiitis of the central nervous system with diffuse cerebral mass effect and giant cells

Primary angiitis of the central nervous system (PACNS), also called primary CNS vasculitis, is an idiopathic inflammatory condition affecting only intracranial and spinal cord vessels, particularly medium-sized and smaller arteries and arterioles. Angiography and histopathology typically do not reveal evidence of systemic vasculitis.[1], [2] Histopathology usually reveals granulomatous inflammation affecting arterioles and small arteries of the parenchyma and/or leptomeninges, similar to that seen in Takayasu’s or giant cell arteritis.[1], [2], [3] We report a patient with biopsy-proven PACNS with giant cells and cerebral mass effect on MRI. Magnetic resonance angiography and cerebral angiography appeared normal and there was no evidence of extracranial vasculitis.     

Multiple brain infarcts in zoster infection

The clinical, CSF, CCT and PET findings in a 14-year-old female patient are reported. CCT and PET investigations demonstrated multiple cerebral infarctions; CSF examinations revealed inflammatory changes. Zoster antibodies were synthesized intrathecally, as detected by an ELISA after adjusting serum and CSF to identical IgG concentrations. Therefore the diagnosis of a cerebral zoster angiitis was made. Diagnostic and therapeutic problems of inflammatory vascular lesions are discussed.