Looks like a stroke, acts like a stroke, but it's more than a stroke: a case of cerebral mucormycosis.

Mucormycosis is a fungus that exhibits angiocentric growth and can cause a thrombotic arteritis. Infection with this organism is uncommon and cerebral involvement is most often secondary to direct invasion through the paranasal sinuses. Here, we present a case of mucormycosis with cerebral involvement without sinus disease, which resulted in ischemic stroke with rapid progression resulting in death.

Activity and damage in granulomatosis with polyangiitis.

AIM: To retrospectively analyze disease activity and damage-associated factors in granulomatosis with polyangiitis (GPA) in Turkey. METHOD: A retrospective analysis was carried out in 21 GPA patients. Assessments for activity were performed with the Birmingham Vasculitis Activity Score for GPA (BVAS/GPA) and for permanent organ damage by the Vasculitis Damage Index (VDI). RESULTS: Lower BVAS/GPA (P = 0.002), absence of renal involvement (P = 0.003) and higher creatinine clearence (P = 0.000) at diagnosis increased the likelihood of achieving remission at 6 weeks. Relapses were associated with high creatinine clearence (P = 0.021), low BVAS/GPA (P = 0.014), absence of renal involvement (P = 0.036) and proteinuria (< 0.5/24 h) (P = 0.013) at diagnosis, whereas achieving remission at 6 weeks (P = 0.012) was associated with absence of co-trimoxazole usage (P = 0.038) and less severe clinical subgroup (P = 0.034). Lower cumulative first 6 months of cyclophosphamide and methylprednisolone were associated with earlier (≤ 12 months) relapses (P = 0.048 and P = 0.083, respectively). Baseline damage (VDI ≥ 1) was associated with a delay in diagnosis (P = 0.032), presentation with milder clinical subgroups (P = 0.052) and low serum creatinine (P = 0.013). The increase in VDI in the first 12 months (early damage) constituted most (91%) of the total damage measured at the end of follow-up. CONCLUSIONS: Despite high early remission rates, relapse represents a major problem in localized GPA in our study. Baseline damage was associated with longer diagnostic delay and lower baseline serum creatinine. The initial phase of the disease seems to be the most crucial period for mortality and accumulated damage.

Childhood primary angiitis of the central nervous system.

OBJECTIVE: To analyze the clinical course and magnetic resonance angiographic (MRA) abnormalities in children with primary angiitis of the central nervous system (cPACNS). STUDY DESIGN: Cohort study. PLACE AND DURATION OF STUDY: Neurosciences and Neuroradiology Department of the Children's Hospital, Lahore, from January 2009 to December 2010. METHODOLOGY: The cohort comprised consecutive patients diagnosed as having cPACNS based on clinical findings and identification of arterial stenosis on magnetic resonance angiography (MRA) in the absence of an underlying condition that could cause these findings. The treatment protocol for ischaemic infarcts consisted of induction therapy with intravenous steroids pulses and intravenous immunoglobulin followed by maintenance therapy with azathioprine and low dose aspirin. When indicated, they were treated with anticoagulants at least for 4 weeks along with induction therapy. Patients were followed at a single centre and systemically assessed for clinical presentation, classification of disease as progressive or non-progressive, adverse effects of anticoagulants, aspirin, azathioprine and their hospital course. RESULTS: Sixty-eight children with medium-large vessel cPACNS (62% boys, 38% girls) with mean age of 8.5 ± 3.5 years were enrolled in this study. Motor deficit (70%); headache (64%) and fever (20%) were the commonest symptoms; whereas hemiparesis (60%); seizures 55% (focal 35%, generalized 20%) and decreased conscious level (30%), were the commonest neurological findings. Neuroradiological findings were ischaemic strokes in 50 (73.5%), haemorrhagic strokes in 10 (14.7%) and ischaemic haemorrhagic lesions in 8 cases (11.8%). Angiographically 51 (51/68, 75%) of the cohort had non-progressive (obliterative) and 17 (17/68, 25%) had evidence of progressive arteriopathy at the time of admission. No secondary haemorrhagic lesions were documented among infarcts strokes, which were treated with heparin and oral anticoagulants. Outcome was survival in 56 cases (81.5%) and death in 12 cases (18.5%). All survivors were discharged on long-term oral aspirin; 15 of them were also commenced on azathioprine. Neurological findings among the 56 survivors were; normal 20%, minor disabilities in 25%, moderate disabilities in 20% and severe disabilities in 35%. CONCLUSION: The spectrum of cPACNS includes both progressive and non-progressive forms with significant morbidity and mortality. This treatment protocol of immunosuppressive therapy may improve long-term neurological outcome in children with medium-large vessel childhood primary angiitis of the CNS.

[Primary cerebral vasculitis in children]. / Primaer cerebral vaskulitis hos børn.

INTRODUCTION: Primary cerebral vasculitis in children is a newly recognized, rare inflammatory condition affecting the vessels of the brain. It is characterized by newly acquired neurological deficit(s) with angiographic or histological evidence of central nervous system (CNS) vasculitis, in the absence of other known diseases with these findings. MATERIAL AND METHODS: We performed a retrospective review of children below 15 years submitted with CNS vasculitis to the department between 1999 and 2008. RESULTS: Six (two boys, four girls) of ten children with clinical and vascular imaging findings detected by magnetic resonance were diagnosed with primary CNS vasculitis. Age at onset was three to 12 years. Acutely acquired hemiparesis was seen in five children, two had facial palsy. Among other symptoms were headache, ataxia, dysarthria, loss of consciousness and seizures. Only modest changes in blood and spinal fluid values were seen. On magnetic resonance angiography, varying segmental stenoses were found. All had supratentorial lesions, and in two patients infratentorial lesions were also detected by MRI. Monthly treatment with high-dose intravenous corticosteroids for six months was successful in most of the patients. In two patients with progressive CNS vasculitis, the treatment was supplemented by intravenous cyclophosphamide and azathioprin, respectively. CONCLUSION: Primary CNS vasculitis is an acutely acquired inflammatory disease with severe neurological deficits and sequelae which may have a fatal outcome. Despite this the prognosis is acceptable since event-free survival can be achieved in almost 70% if early immunosuppressive therapy is initiated.

Primary central nervous system vasculitis: analysis of 101 patients.

OBJECTIVE: To analyze the clinical findings, response to therapy, outcome, and incidence of primary central nervous system vasculitis (PCNSV) in a large cohort from a single center. METHODS: We retrospectively studied 101 patients with PCNSV, selected by predetermined diagnostic criteria, who were seen during a 21-year period. This was a collaborative study by five departments at a large multispecialty clinic. Clinical findings and outcomes were compared among patients categorized by method of diagnosis, response to therapy, survival, and degree of disability. An annual incidence rate was calculated. RESULTS: Seventy patients were diagnosed by angiography and 31 by central nervous system biopsy. Three histological patterns were observed during biopsy. Although most patients responded to therapy, an increased mortality rate was observed. Relapses occurred in one fourth of patients. Mortality rate and disability at last follow-up were greater in those who presented with a focal neurological deficit, cognitive impairment, cerebral infarctions, and angiographic large-vessel involvement but were lower in those with prominent gadolinium-enhanced lesions when evaluated by magnetic resonance imaging. The annual incidence rate of PCNSV was 2.4 cases per 1,000,000 person-years. INTERPRETATION: PCNSV is a rare disease that may result in serious neurological outcomes or death. Angiography and brain biopsy may complement each other when determining the diagnosis. Early recognition and treatment may reduce poor outcomes. PCNSV is a variable syndrome that appears to consist of several subsets of heterogeneous diseases.

Outcome of patients with small-vessel vasculitis admitted to a medical ICU.

PURPOSES: This study aims to describe the clinical course and prognostic factors of patients with small-vessel vasculitis admitted to a medical ICU. METHODS: We reviewed the clinical records of 38 patients with small-vessel vasculitis admitted consecutively to the ICU between January 1997 and May 2004. The APACHE (acute physiology and chronic health evaluation) III prognostic system was used to determine the severity of illness on the first ICU day; the sequential organ failure assessment (SOFA) score was used to measure organ dysfunction, and the Birmingham vasculitis activity score for Wegener granulomatosis (BVAS/WG) was used to assess vasculitis activity. Outcome measures were the 28-day mortality and ICU length of stay. RESULTS: Nineteen patients (50%) had Wegener granulomatosis, 16 patients (42%) had microscopic polyangiitis, 2 patients had CNS vasculitis, and 1 patient had Churg-Strauss syndrome. Reasons for ICU admission included alveolar hemorrhage in 14 patients (37%), sepsis in 5 patients (13%), seizures in 3 patients (8%), and pneumonia in 2 patients (5%). The median ICU length of stay was 4.0 days (interquartile range, 2.0 to 6.0 days). The APACHE III score was lower in survivors than nonsurvivors (p = 0.010). The predicted hospital mortality was 54% for nonsurvivors and 21% for survivors (p = 0.0038). The mean SOFA score was 11.6 (SD, 2.6) in nonsurvivors, compared to 6.9 (SD, 2.4) in survivors (p = 0.0004). Mean BVAS/WG scores were 8.6 (SD, 3.6) in nonsurvivors and 4.7 (SD, 4.6) in survivors (p = 0.0889). Twenty-six percent of the patients received invasive mechanical ventilation, and 33% underwent dialysis. The 28-day and 1-year mortality rates were 11% and 29%, respectively. CONCLUSIONS: The mortality of patients with small-vessel vasculitis admitted to the ICU is lower than predicted, and alveolar hemorrhage is the most common reason for ICU admission.

Fatal strokes in patients with rhino-orbito-cerebral mucormycosis and associated vasculopathy.

Within a 10-y period, fatal strokes occurred during parenteral administration of amphotericin B and surgical debridement of paranasal sinuses in 6 pathologically verified cases of rhino-orbito-cerebral mucormycosis (ROCM). All patients had unnoticed type-2 diabetes mellitus without ketoacidosis. They presented with unilateral orbital cellulitis and cavernous sinus syndrome. Fatal malignant cerebral infarctions occurred in the carotid system in 5 patients, and in the basilar artery or its major branches in 2 patients. Accelerated thrombotic occlusion of the cavernous portion of the carotid artery or the basilar artery was likely to be due to mucormycosis associated-vasculopathy and diabetic vasculopathy. One patient died of massive subarachnoid hemorrhage following rupture of the mycotic aneurysm. Despite parenteral administration of amphotericin B, fatal outcome of ROCM in patients with unnoticed diabetes mellitus occurs due to mucormycosis-associated malignant strokes. To improve outcome, a combination of early radical debridement, ocular exenteration, parenteral and local administration of amphotericin B, and decompression craniotomy should be considered.

High proteinase 3-anti-neutrophil cytoplasmic antibody (ANCA) level measured by the capture enzyme-linked immunosorbent assay method is associated with decreased patient survival in ANCA-associated vasculitis with renal involvement.

Wegener granulomatosis (WG) and microscopic polyangiitis (MP), diseases associated with antineutrophil cytoplasmic antibodies (ANCA), had an extremely poor prognosis before the introduction of cyclophosphamide and corticosteroids for their treatment. However, there is still reduced patient survival, and some studies have documented severe side effects of the immunosuppressants used. This 10-yr follow-up study assessed 117 consecutive patients with WG or MP with biopsy-confirmed renal involvement. The cumulative relative patient survival was lower: 0.664 for women and 0.648 for men. The causes of death (n = 64) were in most cases registered as associated with the vasculitic disease. Analysis of possible predictive factors for patient survival by multiple Cox regression analysis revealed that a very high level of proteinase 3 (PR3)-ANCA measured by the capture ELISA method, a diagnosis of MP, and older age were factors predicting poorer patient survival. High levels of B-thrombocytes at time of diagnosis were associated with a better prognosis. For patients surviving the first year, remission-sustaining therapy with azathioprine for longer than 12 mo was associated with improved patient survival. Thirty-nine patients developed end-stage renal failure. Elevated serum creatinine at time of diagnosis and a very high level of PR3-ANCA by capture ELISA were factors predicting a higher risk for renal failure during follow-up. The epitope on PR3 assessed by capture ELISA needs to be further analyzed and explored: it seemed to implicate poorer patient and renal survival in WG or MP with renal involvement.

Prognosis of patients with suspected primary CNS angiitis and negative brain biopsy.

The authors retrospectively analyzed 25 patients who had a nondiagnostic brain biopsy for clinically suspected primary CNS angiitis to determine the effect of immunosuppressive therapy on 1-year outcome. Good outcome was seen in 6 of 10 treated patients and in 8 of 15 untreated patients (p= 0.93). These findings do not indicate that the addition of immunosuppressive therapy significantly enhances outcome of patients with clinically suspected primary angiitis of the CNS and a nondiagnostic brain biopsy.