Autosomal-dominant early-onset spastic paraparesis with brain calcification due to IFIH1 gain-of-function.

We describe progressive spastic paraparesis in two male siblings and the daughter of one of these individuals. Onset of disease occurred within the first decade, with stiffness and gait difficulties. Brisk deep tendon reflexes and extensor plantar responses were present, in the absence of intellectual disability or dermatological manifestations. Cerebral imaging identified intracranial calcification in all symptomatic family members. A marked upregulation of interferon-stimulated gene transcripts was recorded in all three affected individuals and in two clinically unaffected relatives. A heterozygous IFIH1 c.2544T>G missense variant (p.Asp848Glu) segregated with interferon status. Although not highly conserved (CADD score 10.08 vs. MSC-CADD score of 19.33) and predicted as benign by in silico algorithms, this variant is not present on publically available databases of control alleles, and expression of the D848E construct in HEK293T cells indicated that it confers a gain-of-function. This report illustrates, for the first time, the occurrence of autosomal-dominant spastic paraplegia with intracranial calcifications due to an IFIH1-related type 1 interferonopathy.

Diversity in anti-N-methyl-D-aspartate receptor encephalitis: case-based evidence.

Antibodies against N-methyl-D-aspartate receptor (NMDAR) are identified in the form of immune-mediated encephalitis in which typical manifestations include neuropsychiatric symptoms, seizures, abnormal movements, dysautonomia and hypoventilation. The authors report two cases of anti-NMDAR encephalitis with different presentations and patterns of progression. The first patient presented with status epilepticus and later developed psychosis, pyramidal signs and diffuse encephalopathy. The second patient presented with acute psychosis followed a week later by seizures, dystonia, rigidity, oromandibular dyskinesias and dysautonomia. Possible mechanisms responsible for the clinical manifestations of this disease are discussed in light of recently described additional clinical and laboratory findings.

Cerebral Venous Thrombosis Due to Overdrainage in a Patient With Normal Pressure Hydrocephalus: A Case Report.

Mechanical shunting of cerebrospinal fluid (CSF) is an effective treatment for hydrocephalus but is not exempt from complications. A 67-year-old male with a history of normal pressure hydrocephalus (NPH) and ventriculoperitoneal shunting (VPS) one year ago presented with gait disturbance and memory impairment. His head computed tomography (CT) was normal, and the shunting pressure was reduced from 110 to 70 mmH20 with gait and memory improvement. One week later, he reported persistent pressure headaches, which worsen when lying down, accompanied by nausea and vomiting. His neurological examination was notable for a short-stepped wide-based gait. Two generalized seizures were observed. CT cerebral venography revealed sinus venous thrombosis (SVT). After two days, a new CT was performed, and bilateral subdural hygromas were found. The shunting pressure was readjusted to 110 mmH20, and symptom improvement was noted. One week later, CT showed enlargement and bleeding of subdural collections. The drainage system was closed, and the patient continue to recover. The temporal association between pressure adjustment and symptom onset and the evidence of progressive subdural effusions suggest that the decrease of CSF volume by overdrainage led to an increase in cerebral blood volume and the dilatation of the venous sinus, which precipitated thrombus formation.

Gradenigo's Syndrome with Carotid Septic Stenosis.

Gradenigo's syndrome was firstly described in 1907 by Giusseppe Gradenigo and is defined as the clinical triad of suppurative otitis media, ipsilateral abducens nerve palsy, and pain in the distribution of the first and the second branches of the trigeminal nerve. Since the advent of antibiotics, the incidence of this potentially life-threatening complication has diminished, but occasional cases still occur. We herein report a pediatric case of otitis media associated with Gradenigo's syndrome complicated by ipsilateral septic cavernous sinus thrombosis and infectious arteritis of the internal carotid artery.

Screening for Pompe disease in a Portuguese high risk population.

Pompe disease is a rare metabolic disorder with available enzymatic replacement therapy. Contrasting with the classic infantile form, the others subtypes have a heterogeneous presentation that makes an early and accurate diagnosis difficult. We conducted a prospective, multicenter, observational study to identify undiagnosed patients. During a one-year period, patients followed in Portuguese neuromuscular outpatient clinics with proximal muscle weakness affecting upper and/or lower limbs, hyperCKemia in two or more determinations or hypotonia and hyperCKemia, were screened for acid α-glucosidase deficiency by dried blood spots. Lysosomal acid-alpha-1,4-glucosidase activity was determined by tandem mass spectrometry and positive results were confirmed by molecular study. From the 99 patients screened, Pompe disease was confirmed in 4, with age of onset ranging from 2.5 to 48 years, all with limb girdle muscle weakness, corresponding to a frequency of 4% in our cohort and 4.9% of limb girdle muscle weakness. Screening for Pompe disease in high risk populations, using dried blood spots, was already performed in some European populations. Apart from two negative Scandinavian studies, positive cases were confirmed in 2.8-7.9% of patients presenting with limb girdle muscle weakness and in 0-2.5% with isolated hyperCKemia.

Isolated velopalatine paralysis associated with parvovirus B19 infection.

A case of isolated velopalatine paralysis in an 8-year-old boy is presented. The symptoms were sudden-onset of nasal speech, regurgitation of liquids into the nose and dysphagia. Brain MRI and cerebrospinal fluid examination were normal. Infectious serologies disclosed an antibody arrangement towards parvovirus B19 that was typical of recent infection. In the absence of other positive data, the possibility of a correlation between the tenth nerve palsy and parvovirus infection is discussed.

Localized scleroderma en coup de sabre in the Neurology Clinic.

BACKGROUND: Localized scleroderma en coup de sabre (LScs) is a form of localized scleroderma thought to be an autoimmune disorder. Central nervous system involvement is not rare and neurological manifestations include seizures, focal neurological deficits, headache and neuropsychiatric changes. METHODS: Patients attending the Neurology Clinic with the final diagnosis of LScs with neurological manifestations were identified and clinical and imagiological records reviewed. RESULTS: Five patients (0.024%) had LScs with neurological involvement, presenting with transient focal neurologic deficits, seizures, headache or migraine with aura. Neuroimaging studies confirmed localized skin depression and showed bone thinning, white matter lesions, brain calcifications, sulcal effacement and meningeal enhancement. Three patients experienced clinical improvement after immunosuppressive therapy, and in two of these patients neuroimaging findings also improved. CONCLUSIONS: Recognizing typical dermatologic changes is keystone for the diagnosis of LScs with neurological involvement. It is a diagnosis of exclusion and extensive etiological diagnostic evaluation should be performed. Treatment options, including conservative follow-up or immunosuppressive therapy, should be carefully considered.

Dramatic recovery after IV thrombolysis in anterior circulation ischemic stroke: predictive factors and prognosis.

BACKGROUND AND PURPOSE: Dramatic recovery (DR) after thrombolysis is dependent of vessel recanalization and is predictive of favorable clinical outcome. Successful recanalization is not equivalent to DR. Our objective was to assess its frequency and evaluate clinical and biochemical predictors and their prognosis. METHODS: We analyzed prospectively registered data from January 2007 to September 2012. All patients with anterior circulation stroke and NIHSS≥10 were included. Improvement of ≥10 or a score ≤3 24h after thrombolysis was defined as DR. RESULTS: In the 230 patients included, DR frequency was 23% (53 patients). DR group had lower admission NIHSS (14 vs 17, p=0.024), less total anterior circulation infarcts (p=0.009), more partial anterior circulation infarcts (p=0.003) and lower blood glucose on admission (118 vs 128mg/dL, p=0.013). All patients with DR had an Alberta Stroke Program Early CT Score (ASPECTS) ≥7, vs 89.3% without DR (p=0.013). Arterial recanalization, defined as hyperdense middle cerebral artery sign disappearance on control CT, was more frequent in the DR group (68.4% vs 14.1%, p<0.001). Intracranial hemorrhage on 24h-control CT scan was less frequent in the DR group (p<0.001). Multinomial logistic regression analysis showed that ASPECTS score was an independent predictor of DR (OR=2.35, 95%CI=1.32-4.16, p=0.003) and CT evidence of recanalization was independently associated with DR (OR=11.60, 95%CI, 3.02-44.53, p<0.001). CONCLUSION: DR is a frequent occurrence. ASPECTS score is an independent predictor of DR, which is also independently associated with CT evidence of middle cerebral artery recanalization.

Intravenous thrombolysis is more effective in ischemic cardioembolic strokes than in non-cardioembolic?

UNLABELLED: It was suggested that intravenous thrombolysis (IT) leads to larger extent recanalization in cardioembolic stroke. In this work we assess if this has beneficial clinical traduction. METHOD: We evaluated 177 patients undergoing IT, which were categorized into cardioembolic (CE) and non-cardioembolic (NCE). National Institutes of Health Stroke Scale (NIHSS) and modified Rankin scale were compared. RESULTS: The mean age was 67.4 ± 12.01 and 53.8% were male. The mean NIHSS was: 14 (admission), 9 (24 h) and 6 (discharge), similar in subgroups. The difference between NIHSS at admission and 24 hours was 4.17 ± 4.92 (CE: 4.08 ± 4.71; NCE: 4.27 ± 5.17, p=0.900) and at admission and discharge there was an average difference of 6.74 ± 5.58 (CE: 6.97 ± 5.68; NCE: 6.49 ± 5.49, p=0.622). The mRS at discharge and 3 months was not significantly different by subtype, although individuals whose event was NCE are more independent at 3 months. CONCLUSION: Ours findings argue against a specific paper of IT in CE. It can result from heterogeneity of NCE group.

Diffusion-weighted magnetic resonance imaging findings in a patient with cerebral syphilitic gumma.

Cerebral syphilitic gummas are rare entities, consisting of masses of granulation tissue that result from an exacerbated cell-mediated inflammatory response to Treponema pallidum, usually arising from the meninges of the convexity. Conventional magnetic resonance imaging and computed tomography findings of cerebral gummas have been reported, but diffusion-weighted imaging findings have not been previously described. In our patient, magnetic resonance imaging revealed a juxtacortical lesion with nodular enhancement, moderately restricted diffusion, a dural tail, and surrounding vasogenic edema. The role of diffusion-weighted imaging findings in the diagnosis of this condition is underscored.

[Wallerian degeneration after stroke: a new prognostic factor?]. / Degenerescência Walleriana pós-enfarte: um novo factor prognóstico?

Wallerian degeneration (WD) after ischemic stroke has been associated to persistent motor impairment, but signal intensity changes on conventional magnetic resonance imaging (MRI) are generally not detected until four weeks after the event. We report a 54 year old male patient, referred to our hospital for sudden-onset left hemiparesis. Cerebral CT showed right fronto-parietal infarct (middle cerebral artery stroke). We performed two CT control, which revealed no haemorrhagic transformation. MRI, obtained 13 days after the onset, demonstrated the infarct, mainly subcortical, extending throughout fronto-temporo-parietal areas and restricted diffusion in the ipsilateral corticospinal tract. In conclusion, WD is apparent on diffusion-weighted imaging within two weeks of stroke, allowing a better prognostic evaluation of recovery. The abnormal signal should not be misinterpreted as new ischaemic lesions.

Intravenous thrombolysis is more effective in ischemic cardioembolic strokes than in non-cardioembolic? / A trombólise endovenosa é mais eficaz nos acidentes vasculares cerebrais isquêmicos cardioembólicos do que nos não cardioembólicos?

It was suggested that intravenous thrombolysis (IT) leads to larger extent recanalization in cardioembolic stroke. In this work we assess if this has beneficial clinical traduction. METHOD: We evaluated 177 patients undergoing IT, which were categorized into cardioembolic (CE) and non-cardioembolic (NCE). National Institutes of Health Stroke Scale (NIHSS) and modified Rankin scale were compared. RESULTS: The mean age was 67.4±12.01 and 53.8 percent were male. The mean NIHSS was: 14 (admission), 9 (24 h) and 6 (discharge), similar in subgroups. The difference between NIHSS at admission and 24 hours was 4.17±4.92 (CE: 4.08±4.71; NCE: 4.27±5.17, p=0.900) and at admission and discharge there was an average difference of 6.74±5.58 (CE: 6.97±5.68; NCE: 6.49±5.49, p=0.622). The mRS at discharge and 3 months was not significantly different by subtype, although individuals whose event was NCE are more independent at 3 months. CONCLUSION: Ours findings argue against a specific paper of IT in CE. It can result from heterogeneity of NCE group.

Alguns estudos sugerem que a trombólise endovenosa (TE) conduz a melhor recanalização nos acidentes vasculares cerebrais isquêmicos (AVCI) cardioembólicos. Neste trabalho questionamos se isto terá tradução em benefício clínico. MÉTODO: Avaliamos 177 doentes submetidos a TE, os quais foram categorizados como cardioembólicos (CE) e não cardioembólicos (NCE). Compararam-se a National Institutes of Health Stroke Scale (NIHSS) e escala de Rankin modificada. RESULTADOS: A idade média foi 67,4±12,01 e 53,8 por cento eram homens. NIHSS média foi: 14 (admissão), 9 (24 h), 6 (alta), semelhante nos subgrupos. A diferença entre NIHSS à admissão e 24 h foi de 4,17±4,92 (CE: 4,08±4,71; NCE: 4,27±5,17, p=0,900) e entre a admissão e a alta de 6,74±5,58 (CE: 6,97±5,68; NCE: 6,49±5,49, p=0,622). A classificação na mRS não foi significativamente diferente nos subgrupos (alta e 3 meses), mas os doentes com eventos NCE estavam mais independentes aos 3 meses. CONCLUSÃO: Os nossos resultados não documentam um papel específico da TE nos CE, o que pode resultar da heterogeneidade do grupo NCE.

Isolated velopalatine paralysis associated with parvovirus B19 infection / Paralisia velopalatina isolada associada a infecção por parvovírus B 19

A case of isolated velopalatine paralysis in an 8-year-old boy is presented. The symptoms were sudden-onset of nasal speech, regurgitation of liquids into the nose and dysphagia. Brain MRI and cerebrospinal fluid examination were normal. Infectious serologies disclosed an antibody arrangement towards parvovirus B19 that was typical of recent infection. In the absence of other positive data, the possibility of a correlation between the tenth nerve palsy and parvovirus infection is discussed.

Apresentamos um caso de paralisia velopalatina isolada, num menino de 8 anos, que se manifestou por voz nasalada, regurgitação de líquidos pelo nariz e disfagia, de início súbito. A ressonância magnética encefálica e o estudo do líquido cefalo-raquidiano foram normais. O perfil serológico dos anticorpos anti-parvovírus B19 era típico de infecção recente. Na ausência de outros dados positivos, discute-se a possibilidade de uma correlação entre a parésia do X nervo e a infecção por parvovírus.