Peter Berlit

Diagnosis and treatment of cerebral vasculitis

Vasculitides are characterized by inflammation and necrosis of the blood vessel wall. Large vessels including the aorta are affected in giant-cell arteritis, medium-size arteries in classic polyarteritis nodosa. The small-vessel vasculitides are separated in those with antineutrophil cytoplasm antibodies (ANCA) and those without. The primary angiitis of the central nervous system (PACNS) is a rare disorder affecting both medium- and small-sized vessels. Major symptoms of cerebral vasculitis are stroke, headache and encephalopathy. Diagnosis is based on laboratory and imaging findings. When cerebral affection occurs in systemic vasculitis an acute inflammatory response with raised erythrocyte sedimentation rate and increased values of C-reactive protein is present. In many cerebral vasculitides including PACNS, CSF studies reveal inflammatory findings. Magnetic resonance imaging, including ADC maps, diffusion and gradient echo sequences, is the investigation of choice to detect and monitor cerebral involvement. Certain MRI techniques and 18-fluorodeoxyglucose positron emission tomography allow the visualization of vessel wall inflammation when the lumen is still unaffected on angiography. The treatment recommendations for cerebral angitis are derived from protocols for systemic vasculitides. In general, a combination of steroids and pulse cyclophosphamide (CYC) is recommended for induction treatment. An alternative option is the use of the anti- CD20 antibody rituximab. Methotrexate, azathioprine and mycophenolate mofetil are recommended as alternatives to CYC once remission is achieved.

Cerebral vasculitis in adults: what are the steps in order to establish the diagnosis? Red flags and pitfalls

Cerebral vasculitis is a rare cause of juvenile stroke. It may occur as primary angiitis of the central nervous system (PACNS) or as CNS manifestation in the setting of systemic vasculitis. Clinical hints for vasculitis are headache, stroke, seizures, encephalopathy and signs of a systemic inflammatory disorder. Diagnostic work‐up includes anamnesis, whole body examination, laboratory and cerebral spinal fluid (CSF) studies, magnetic resonance imaging (MRI), angiography and brain biopsy. Due to the rarity of the disease, exclusion of more frequent differential diagnoses is a key element of diagnostic work ‐up. This review summarizes the steps that lead to the diagnosis of cerebral vasculitis and describes the red flags and pitfalls. Despite considering the dilemma of angiography‐negative vasculitis and false‐negative brain biopsy in some cases, it is important to protect patients from ‘blind’ immunosuppressive therapy in unrecognized non‐inflammatory differential diagnosis.

Neurologic complications of acute and chronic renal disease

There is an increasing incidence and prevalence of patients with chronic kidney disease (CKD) in Western industrialized countries and currently is estimated at approximately 10% of adults aged over 20 years. Renal failure causes an excessively increased risk of cerebrovascular and cardiovascular complications. Moreover, renal failure leads to a number of the neurologic symptoms neurologists are often confronted with. This chapter gives an overview of possible neurologic complications of acute renal failure and CKD. Complications of the central nervous system (e.g., uremic encephalopathy, disequilibrium syndrome, and drug induced disorders) are reviewed. It has long been known that uremia leads to peripheral nerve injury. Frequent neurological diseases such as uremic polyneuropathy, autonomic neuropathy, and a range of mononeuropathies are discussed.

Retinal pathology in idiopathic moyamoya angiopathy detected by optical coherence tomography.

Objective: To investigate whether patients with moyamoya angiopathy without obvious retinal pathologies such as retinal infarctions or the congenital morning glory anomaly may have subtle subclinical retinal changes. Methods: In this cross-sectional study, spectral domain optical coherence tomography was used to analyze the retinal morphology of 25 patients with idiopathic moyamoya angiopathy and 25 age- and sex-matched healthy controls. We analyzed the retinal vasculature with blue laser autofluorescence, lipofuscin deposits with MultiColor confocal scanning laser ophthalmoscopy, and the optic nerve head (ONH) volume with a custom postprocessing algorithm. In addition to the total retinal thickness, semiautomated segmentation was used for segmentation of retinal layers in macular cross scans, macular volume scans, and peripapillary ring scans. Results: The main finding was a pronounced reduction of the ONH volume in moyamoya angiopathy compared with controls (0.76 ± 0.45 mm3 and 1.47 ± 0.50 mm3, respectively; p < 0.0001), which was associated with a less pronounced reduction of the retinal nerve fiber layer in macular volume scans (0.97 ± 0.11 mm3 and 1.10 ± 0.10 mm3, respectively; p < 0.001). Autofluorescence and MultiColor confocal scanning laser ophthalmoscopy images revealed no pathologies except for one branch retinal artery occlusion. Conclusion: Our results indicate that even patients with moyamoya angiopathy who do not have obvious retinal abnormalities have retinal abnormalities. These can be detected by spectral domain optical coherence tomography, and the association of ONH abnormalities with the vascular changes may suggest that idiopathic moyamoya angiography is a systemic disease involving abnormalities of the early mesodermal development.

Primary central nervous system vasculitis and its mimicking diseases – clinical features, outcome, comorbidities and diagnostic results – A case control study

OBJECTIVES To compare clinical features and outcome, imaging characteristics, biopsy results and laboratory findings in a cohort of 69 patients with suspected or diagnosed primary central nervous system vasculitis (PCNSV) in adults; to identify risk factors and predictive features for PCNSV. PATIENTS AND METHODS We performed a case-control-study including 69 patients referred with suspected PCNSV from whom 25 were confirmed by predetermined diagnostic criteria based on biopsy (72%) or angiography (28%). Forty-four patients turned out to have 15 distinct other diagnoses. Clinical and diagnostic data were compared between PCNSV and Non-PCNSV cohorts. RESULTS Clinical presentation was not able to discriminate between PCNSV and its differential diagnoses. However, a worse clinical outcome was associated with PCNSV (p=0.005). Biopsy (p=0.004), contrast enhancement (p=0.000) or tumour-like mass lesion (p=0.008) in magnetic resonance imaging (MRI), intrathecal IgG increase (p=0.020), normal Duplex findings of cerebral arteries (p=0.022) and conventional angiography (p 0.010) were able to distinguish between the two cohorts. CONCLUSION In a cohort of 69 patients with suspected PCNSV, a large number (64%) was misdiagnosed and partly received treatment, since mimicking diseases are very difficult to discriminate. Clinical presentation at manifestation does not help to differentiate PCNSV from its mimicking diseases. MRI and cerebrospinal fluid analysis are unlikely to be normal in PCNSV, though unspecific if pathological. Cerebral angiography and biopsy must complement other diagnostics when establishing the diagnosis in order to avoid misdiagnosis and mistreatment. CLINICAL TRIAL REGISTRATION German clinical trials register: http://drks-neu.uniklinik-freiburg.de/drks_web/, Unique identifier: DRKS00005347.

D313Y mutation in the differential diagnosis of white matter lesions: Experiences from a multiple sclerosis outpatient clinic

White matter lesions (WML) in younger patients might be due to a variety of neurological disorders. Fabry disease (FD), an x-linked inherited lysosomal storage disorder, happens to be misdiagnosed as multiple sclerosis (MS). In two middle-aged female patients, presenting bilateral WML, diagnosis of MS turned out to be doubtful. Human genetic analysis presented the Fabry mutation D313Y, in which clinical impact is still unclear. Disease manifestations outside the central nervous system were not detected. Our findings support the suspicion that Fabry mutation D313Y may be involved in neural damage resulting in WML.

Ventricular Microaneurysms in Moyamoya Angiopathy Visualized with 7T MR Angiography

SUMMARY: The pathophysiologic role of hemodynamic alteration to peripheral vessels in Moyamoya angiopathy and the formation of microaneurysms remains unclear. The purpose of this study was to investigate microaneurysms in collateral Moyamoya vessels by using 7T ultra-high-field MR imaging. Ten patients with Moyamoya disease were evaluated with TOF-MRA at 7T acquired with 0.22 × 0.22 × 0.41 mm3 resolution. In 10 patients, 4 microaneuryms located in the ventricles were delineated. The mean diameters of collateral vessels and microaneurysms arising from those vessels were 0.87 mm (range, 0.79–1.07 mm) and 0.80 mm (range, 0.56–0.96 mm), respectively. In 1 case with follow-up scans 6 months after a direct extracranial-intracranial bypass operation, the microaneurysm disappeared. Ventricular microaneurysms in Moyamoya angiopathy collateral vessels, inaccessible by conventional imaging techniques, can be detected by 7T TOF-MRA.

Reversible cerebral vasoconstriction syndrome associated with fingolimod treatment in relapsing–remitting multiple sclerosis three months after childbirth

Reversible cerebral vasoconstriction syndrome (RCVS) is characterized by acute thunderclap headache, evidence of vasoconstriction in conventional angiography or magnetic resonance angiography and reversibility of these phenomena within 12 weeks. Some triggering factors, for example drugs such as selective serotonin reuptake inhibitors, sumatriptan, tacrolimus, cyclophosphamide and cocaine, or states such as pregnancy, puerperium or migraine have been described. We describe the case of a 29-year-old woman with RCVS associated with fingolimod three months after childbirth. This case represents the first report of RCVS in fingolimod treatment.

Klinische Anwendung der TCCD zum Nachweis intrakranieller Aneurysmen

ZusammenfassungInnerhalb eines Zeitraumes von 15 Monaten wurden 88 Patienten mit 102 angiographisch nachgewiesenen intrakraniellen Aneurysmen unter Verwendung einer 2-MHz-Sonde mit der transkraniellen farbkodierten Duplexsonographie (TCCD) untersucht. Es wurden die Größe und der genaue Aneurysmasitz bestimmmt. Insgesamt konnten 70 (77%) Aneurysmen mit einem Durchmesser von 16±8 mm (6–55 mm) dargestellt werden. Eine sehr gute Darstellung der Aneurysmen gelang bei 36 (42%), eine mäßige bei 34 (40%) Aneurysmen, 16 (16%) Aneurysmen konnten trotz ausreichender Bildqualität nicht dargestellt werden. Bei weiteren 16 (16%) Aneurysmen war kein ausreichendes Knochenfenster vorhanden. Thrombosierte Anteile innerhalb der Aneurysmen konnten bei 16 (75%) von 20, der mit Coils behandelte Anteil bei 12 (48%) von 25 Aneurysmen erfolgreich dokumentiert werden. Die Methode ist zum Nachweis von teilthrombosierten Anteilen, von Behandlungserfolgen nach Coilembolisation und zur Verlaufskontrolle nicht behandelbarer Aneurysmen geeignet. Die Darstellbarkeit kleiner Aneurysmen ist begrenzt durch das Auflösungsvermögen und die teilweise ungünstigen Beschallungswinkel, somit eignet sich die TCCD nicht als Screeningmethode zum Nachweis von Aneurysmen.SummaryWe investigated 88 Patients with a total of 102 angiographically diagnosed intracranial aneurysms by means of transcranial colour coded Duplex sonography (TCCD) during a time period of 15 months. Both the size and teh localization of teh aneuryms were determined. Seventy aneurysms (77%) with a diameter of 16±8 mm (6-55mm) were detectable, with excellent visualization in 36 (42%), moderate visualization in 34 (40%), and no sufficient visualization in 16 (16%) aneurysms, respectively. In another 16 cases (16%) there was no sufficient vone window. Thrombotic material inside the aneurysm was detectable in 16/20 cases (75%), visualization of coil embolized aneurysms in 12/25 patients (48%). TCCD allows the follow up of cerebral aneurysms, with the detection of thrombosis and treatment effects after embolization. The method is not valid for the detection of intracranial aneurysms

Vasculitic multiplex mononeuritis: polyarteritis nodosa versus cryoglobulinemic vasculitis

A 76-year-old female patient presented with a progressive motor-sensory multiplex mononeuritis (MM). Combined muscle and nerve biopsy showed the typical findings of a polyarteritis nodosa (PAN). Despite treatment with corticosteroids paresthesias increased and purpura of the legs newly appeared. Hepatitis screening revealed chronic hepatitis C-infection associated with cryoglobulinemia Type II (IgM-kappa Ig A). Finally, we diagnosed a hepatitis C-associated cryoglobulinemic vasculitis based on clinical and laboratory findings.