Search

Cerebral cavernous malformations (CCM) consist of clusters of irregular dilated capillaries and represent the second most common type of vascular malformation affecting the central nervous system. CCM might be asymptomatic or cause cerebral hemorrhage, seizures, recurrent headaches and focal neurologic deficits. Causative mutations underlining CCM have been reported in three genes: KRIT1/CCM1, MGC4607/CCM2 and PDCD10/CCM3. Therapeutic avenues are limited to surgery. Here we present clinical, neuroradiological and molecular findings in a cohort of familial and sporadic CCM patients. Thirty subjects underwent full clinical and radiological assessment. Molecular analysis was performed by direct sequencing and MLPA analysis. Twenty-eight of 30 subjects (93%) experienced one or more typical CCM disturbances with cerebral/spinal hemorrhage being the most common (43%) presenting symptom. A molecular diagnosis was achieved in 87% of cases, with three novel mutations identified. KRIT1/CCM1 patients displayed higher risk of de novo CCMs appearance and bleedings. Magnetic Resonance Imaging (MRI) showed that infratentorial region was more frequently affected in mutated subjects while brainstem was often spared in patients with negative genetic testing.

Since the end of February 2020, Italy has suffered one of the most severe outbreaks of coronavirus disease 2019 (COVID-19). However, what happened just before the Italian index case has not yet been investigated. To answer this question, we evaluated the potential impact of COVID-19 on the clinical features of a cohort of neurological inpatients admitted right before the Italian index case, as compared to the same period of the previous year. Demographic, clinical, treatment and laboratory data were extracted from medical records. The data collected included all inpatients who had been admitted to the Neurology and Stroke Units of the Ospedale Maggiore Policlinico, Milan, Italy, from December 15, 2018 to February 20, 2019 and from December 15, 2019 to February 20, 2020. Of the 248 patients, 97 subjects (39.1%) were admitted for an acute cerebrovascular event: 46 in the 2018/2019 period (mean [SD] age, 72.3 [15.6] years; 22 men [47.8%]), and 51 in the 2019/2020 interval (mean [SD] age, 72.8 [12.4] years; 24 men [47.1%]). The number of cryptogenic strokes has increased during the 2019–2020 year, as compared to the previous year (30 [58.8%] vs. 18 [39.1%], p = 0.05). These patients had a longer hospitalization (mean [SD] day, 15.7 [10.5] days vs. mean [SD] day, 11.7 [7.2] days, p = 0.03) and more frequent cerebrovascular complications (9 [30.0%] vs. 2 [11.1%]), but presented a lower incidence of cardiocerebral risk factors (18 [60.0%] vs. 14 [77.8%]). Right before the Italian index case, an increase in cryptogenic strokes has occurred, possibly due to the concomitant COVID-19.

Pseudoxanthoma elasticum is a rare cause for ischaemic stroke. Little is known about acute and secondary prevention strategies in these subjects given the increased risk of gastrointestinal and urinary bleedings. Here we present the case of a 62 years old man affected by pseudoxanthoma elasticum who presented with acute ischaemic stroke and was successfully treated with intravenous thrombolysis. Neurological signs improved after intravenous thrombolysis without bleeding complication. To our knowledge, this is the first case of pseudoxanthoma elasticum—related stroke undergoing intravenous thrombolysis.

Background Hereditary hemorrhagic telangiectasia (HHT), also known as Rendu-Osler-Weber syndrome, is a rare disorder characterized by recurrent epistaxis, telangiectasias and systemic arteriovenous malformations (AVMs). HHT is associated with mutations in genes encoding for proteins involved in endothelial homeostasis such as ENG (endoglin) and ACVRL1 (activin receptor-like kinase-1). Case presentation Here we describe a 22-year-old male presenting with a transient episode of slurred speech and left arm paresis. Brain MRI displayed polymicrogyria. A right-to-left shunt in absence of an atrial septum defect was noted. Chest CT revealed multiple pulmonary AVMs, likely causing paradoxical embolism manifesting as a transient ischemic attack. The heterozygous ENG variant, c.3G > A (p.Met1lle), was detected in the patient. This variant was also found in patient’s mother and in his younger brother who displayed cortical dysplasia type 2. Conclusions The detection of cortical development malformations in multiple subjects from the same pedigree may expand the phenotypic features of ENG-related HHT patients. We suggest considering HHT in young patients presenting with acute cerebral ischemic events of unknown origin.

This study investigated for the first time brain ischemic involvement in 19 consecutive neurologically asymptomatic PNH patients by non-enhanced cerebral MRI, and by intracranial arterial and venous angio-MRI. Eleven cases (58%, 7 aged 5 mm, and 5 cases a score >4 by the age-related white matter changes (ARWMC) scale. Compared with age and sex-matched controls (1:2 ratio), patients showed an increased frequency of periventricular WM vascular degeneration (32% versus 5.2%, p = 0.04) and of severe lesions (ARWMC scale score >4) (26% versus 2.6%, p = 0.05), and a higher overall ARWMC scale score (3.5 ± 1.07 versus 2.0 ± 0.8, mean ± SD, p

PNH is a rare disorder characterized by hemolytic anemia, marrow failure and thrombosis, due to a deficiency in GPI-anchored proteins. Thrombotic events in PNH are commonly described in hepatic, portal, mesenteric, splenic, and renal veins, along with anecdotic case reports of cerebral venous sinus thrombosis and arterial ischemic strokes. This study was aimed at investigate brain involvement in 19 asymptomatic PNH patients by non-enhanced cerebral magnetic resonance imaging (MRI), and by intracranial arterial and venous angio-MRI. Neuroradiological findings were completed with a neuro-psychiatric evaluation, and correlated with clinical/hematologic features and therapy. Seventeen out of 19 patients were classical hemolytic (63% transfusion dependent before treatment with eculizumab and 1 patient also after), and 2 PNH in the context of aplastic anemia (all transfusion-dependent until treatment with ATG-CyA). Median age at diagnosis was 44 years (range 17-80); asthenia and dyspnea on exertion were present in all patients, abdominal pain in 8, and a thrombotic event in 4. Median Hb was 9.6 g/dL (range 6.7-12.9), LDH 3.7-fold (range 1.2-16.3) over upper limit of normal (ULN), and 73% of patients displayed a clone size greater than 50% GPI negative cells; 10/19 of patients were on eculizumab at the moment of the study. On MRI, 11 subjects showed pathological findings: 9 cases displayed white matter (WM) abnormalities related to chronic ischemic small vessel disease, of whom 6 periventricular WM vascular degeneration, and 8 deep WM focal chronic ischemic lesions (5 cases have both sites involved). Moreover, 1 subject showed a focal abnormality >5 mm and 5 subjects a score > 4 as evaluated in WM and basal ganglia by the age related white matter changes (ARWMC) scale. No subject displayed active or previous bleeding, nor were focal alterations of the basal nuclei by the ARWMC scale found. Two patients (80 and 81 yrs) showed atrophy of the cerebral hemispheres. Regarding vascular abnormalities, one subject had hypoplastic left transverse sinus with irregularities in the sinus wall, suspected for prior partial venous thrombosis. Three further cases displayed hypoplastic transverse sinus associated with collateral draining cortical veins, indistinguishable from anatomical variants. Intracranial artery stenosis or aneurysm, and Moya-Moya like alterations were not observed. Finally, cerebral MRI was unremarkable in 8/19 subjects. By comparing patients with or without any MRI abnormality (WM and vascular alterations), mean age was significantly higher in the former (60+17 vs 43+8 yrs, mean+SD, p Neurological examination was unremarkable in all patients but one, who complained of progressive rest tremor in his left arm and leg (twelve years after PNH diagnosis), and was diagnosed with possible Parkinson disease. Previous history of neurological disorders was observed in 3 patients: one typical transient global amnesia (at the age of 60), one seizures (at 5 years), and one headache before the diagnosis of PNH. Regarding psychiatric evaluation, 3/18 patients had a psychiatric disorder according to structured clinical interview for axis I DSM-IV-TR disorders (1 generalized anxiety disorder, 1 bipolar disorder type 2, and 1 adjustment disorder as a consequence of PNH diagnosis). No relationship was observed between MRI findings and neuro-psychiatric assessment. In conclusion, brain MRI revealed chronic ischemic and vascular lesions in 58% of asymptomatic PNH patients. Brain MRI is advisable at diagnosis and during the course of the disease, and WM lesion burden may be useful in the decision to start therapy. Disclosures Barcellini: Agios: Consultancy.