Does amantadine improve cognitive recovery in severe disorders of consciousness after aneurysmal subarachnoid hemorrhage? A double-blind placebo-controlled study.

BACKGROUND: Severe disorders of consciousness (sDoC) are a common sequela of aneurysmal subarachnoid hemorrhages (aSAH), and amantadine has been used to improve cognitive recovery after traumatic brain injury. OBJECTIVE: This study evaluated the effect of amantadine treatment on consciousness in patients with sDoC secondary to aSAH. METHODS: This double-center, randomized, prospective, cohort study included patients ≥ 18 years old with sDoC after aSAH from February 2020 to September 2023. Individual patient data of patients were pooled to determine the effect of amantadine, in comparison to placebo. The primary outcomes at 3 and 6 months after the ictus were evaluated using the modified Rankin scale (mRS) and Glasgow outcome scale (GOS). In addition to all-cause mortality, secondary endpoints were assessed weekly during intervention by scores on Rappaport's Disability Rating Scale (RDRS) and Coma Recovery Scale-Revised (CRSR). RESULTS: Overall, 37 patients with sDoC and initial Glasgow Coma Scale (GCS) varying between 3 and 11 were recruited and randomized to amantadine (test group, n = 20) or placebo (control group, n = 17). The average age was 59.5 years (28 to 81 year-old), 24 (65%) were women, and the mean GCS at the beginning of intervention was 7.1. Most patients evolved to vasospasm (81%), with ischemia in 73% of them. The intervention was started between 30 to 180 days after the ictus, and administered for 6 weeks, with progressively higher doses. Neither epidemiological characteristics nor considerations regarding the treatment of the aneurysm and its complications differed between both arms. Overall mortality was 10.8% (4 deaths). During the study, four patients had potential adverse drug effects: two presented seizures, one had paralytic ileus, and another evolved with tachycardia; the medication was not suspended, only the dose was not increased. At data opening, 2 were taking amantadine and 2 placebo. CONCLUSION: Despite some good results associated with amantadine in the literature, this study did not find statistically significant positive effects in cognitive recovery in patients with delayed post-aSAH sDoC. Further large randomized clinical trials in patients' subgroups are needed to better define its effectiveness and clarify any therapeutic window where it can be advantageous.

Pediatric Donut-Shaped Basilar Artery Aneurysm.

Intracranial aneurysms are uncommon in the pediatric population. We present a case of an 11-year-old boy presenting with subarachnoid hemorrhage caused by a "donut-shaped" basilar tip aneurysm. It occurs when the flow geometry produces a circumferential laminar flow into the aneurysmal sac, resulting in a central thrombosis. Optimal management of this type of aneurysm is not already clear, and further studies are needed to clarify the best treatment approach, especially in the pediatric population.

Pediatric intracranial aneurysms in a Southern Brazilian population.

INTRODUCTION: Intracranial aneurysms are rare in the pediatric population, and their diagnosis can be challenging. They differ from their adult counterparts in several aspects, and hemorrhage is the most common presentation. OBJECTIVE: To evaluate clinical data, aneurysm characteristics, and therapeutic results in a series of patients younger than 19 years of age with intracranial aneurysms. METHOD: A retrospective cross-sectional observational study design analyzed medical records and imaging studies. Variables included age, sex, clinical presentation, comorbidities, aneurysmal characteristics, treatment modality, and clinical outcomes. RESULTS: We identified 15 intracranial aneurysms in 11 patients (6 male), with ages ranging from 3 months to 15 years (mean age 5.2 years). Five patients had associated medical conditions, and hemorrhage was the most frequent clinical presentation (45%). Three patients (27%) had multiple aneurysms, and seven aneurysms were fusiform or dysplastic. The internal carotid artery was the most affected site, involved in 47% of cases. Aneurysm size ranged from 2 to 60 mm (mean 16.8 mm), with giant aneurysms in 27%. Seven patients were treated with endovascular procedures, while three aneurysms were clipped. Symptomatic vasospasm requiring angioplasty occurred in two patients and led to worse outcomes. One patient died due to severe aspiration pneumonia and sepsis that precluded treatment. Good functional outcome (modified Rankin scale - mRS ≤ 2) was achieved in all treated patients (91%). CONCLUSION: The patients with aneurysms in this series were mostly male, presented mostly hemorrhagic syndromes, and mainly had internal carotid artery involvement. The outcome of treated patients was favorable, regardless of treatment modality.

Moyamoya Angiopathy and 15q11.2 Gene Deletion Syndrome.

Although the moyamoya angiopathy has already been associated with several genetic and chromosomal alterations, its physiopathologic mechanisms are not completely understood. We report a case of a 7-year-old male with epilepsy, autism spectrum disorder, and delayed psychomotor development whose genetic investigation showed a deletion of the 15q11.2 gene. He presented with sudden neurologic deficits and neuroimaging studies showed cerebral infarctions, bilateral hypoperfusion, and intracranial carotid artery stenosis. Medical treatment with anticonvulsants and antiplatelets was followed by bilateral cerebral revascularization surgery (encephaloduroarteriosynangiosis). There were no seizures nor ischemic events during the follow-up period. The 15q11.2 gene deletion is a rare mutation related to epilepsy, neurodevelopmental disorders, and malformations. Therefore it is noteworthy that the deletion may also be related to other delayed brain diseases still unknown. To our knowledge, this is the first report of moyamoya syndrome with concurrent 15q11.2 gene deletion.

Angiopathy and Stroke Associated with Homocystinuria in Childhood.

A previously healthy 13 year-old boy presented with acute-onset headaches, aphasia and right-sided hemiparesis. Imaging showed cerebral ischemic infarction due to bilateral carotid occlusion, and investigation for stroke etiology diagnosed homocystinuria. Homocystinuria is an autosomal recessive condition that affects the metabolism of the amino acid methionine due to an enzyme deficiency. This disorder involves multiple organs systems, and complications include thromboembolic events, ectopia lentis, mental retardation, and skeletal abnormalities. The early diagnosis and treatment of hyperhomocystinemia can significantly improve outcomes. Therefore, metabolic screening for homocystinuria is strongly recommended for children presenting with stroke.

Moyamoya disease and syndrome: a review.

Moyamoya disease is a chronic occlusive cerebrovascular disease that is non-inflammatory and non-atherosclerotic. It is characterized by endothelial hyperplasia and fibrosis of the intracranial portion of the carotid artery and its proximal branches, leading to progressive stenosis and occlusion, often clinically manifesting as ischemic or hemorrhagic stroke with high rates of morbidity and mortality. On cerebral angiography, the formation of collateral vessels has the appearance of a puff of smoke (moyamoya in Japanese), which became more conspicuous with the refinement of modern imaging techniques. When there is associated disease, it is known as moyamoya syndrome. Treatments are currently limited, although surgical revascularization may prevent ischemic events and preserve quality of life. In this review, we summarize recent advances in moyamoya disease, covering aspects of epidemiology, etiology, presentation, imaging, and treatment strategies.

A doença de moyamoya, ou doença cerebrovascular oclusiva crônica, é uma afecção não inflamatória e não aterosclerótica, caracterizada por hiperplasia endotelial e fibrose dos segmentos intracranianos das artérias carótidas internas e da porção proximal de seus ramos. Isso provoca estenose progressiva e oclusão, frequentemente manifestada clinicamente como isquemia cerebral ou hemorragia intracraniana, com alta morbimortalidade. A formação compensatória de vasos colaterais produz, na angiografia encefálica, um aspecto de nuvem de fumaça (moyamoya, em japonês). Quando existe doença subjacente que possa estar relacionada, a doença recebe o nome de síndrome de moyamoya. Embora a incidência esteja aumentando graças aos novos métodos diagnósticos, as estratégias terapêuticas ainda são limitadas. O diagnóstico precoce permite cirurgias de revascularização cerebral que podem evitar novos acidentes vasculares e melhorar a qualidade de vida. Nesta revisão são apresentados os avanços recentes sobre a doença de moyamoya, citando aspectos de epidemiologia, etiologia, apresentação, exames diagnósticos e tratamento.

Choreoathetosis in Moyamoya Disease.

Moyamoya disease is a cerebral angiopathy characterized by bilateral progressive narrowing of internal carotid arteries, developing collateral vessels with the aspect of a "puff of smoke." The presentation with movement disorders is extremely rare. We present the case of an 11-year-old girl with low academic performance who complained of involuntary movements starting in her right hand. Neurologic examination showed preserved muscle strength and right hemichoreoathetosis. Neuroimaging showed left hemisphere hypoperfusion and a hypertrophic distal lenticulostriate artery. The symptoms were controlled with medications, and cerebral revascularization was performed. Although movement disorders are usually related to cerebral lesions or hypoperfusion, cases without these etiologies were described. Thus the finding of asymmetric lenticulostriate arteries improving after asymmetry reduction suggests a possible role in the pathogenesis. Further studies are needed to fully elucidate the mechanisms between moyamoya disease and movement disorders.

Microanatomic Study of the Optic Canal.

BACKGROUND: The continuous development of microsurgical techniques to treat lesions in and around the optic canal (OC) emphasizes the need for an accurate understanding of the microanatomy of the region. METHODS: Forty anatomic specimens were studied, with emphasis on the OC. The sphenoid bone and related structures were decalcified, added to animal gelatin, cut into 1-mm thick slices, and observed through a surgical microscope. The OC was considered the course that contained exclusively the optic nerve (ON) and ophthalmic artery. RESULTS: The mean distance between the medial walls of the OC was 12.2 mm, and the OC had an average length of 12.06 mm. The OC has a horizontal oval shape in the proximal (internal) segment; a round shape in the middle segment; and a vertical oval shape in the distal (external) segment at the orbital cavity. In the middle segment of the OC, the thickest wall of the OC was the lateral (average: 0.68 mm), while the medial, inferior, and superior wall measures had averages of 0.75, 0.40, and 0.39 mm, respectively. The lateral wall of the sphenoid sinus is located under the OC, and the inferior wall of the OC separates both structures. The ophthalmic artery inside the OC was always located under the ON, between the dural sheaths, and had an average diameter of 1.03 mm. CONCLUSIONS: The neurovascular structures within the OC vary in size and shape. The anatomic knowledge of the OC and its variations allows better surgical results and minimizes the surgical morbidity.

Cervical Disorders in Mucopolysaccharidosis IVA-Morquio disease.

Morquio disease or mucopolysaccharidosis type IVA (Online Mendelian Inheritance in Man No. 253000) is a rare autosomal recessive disease classified in the group of metabolism inborn errors. The glycosaminoglycans accumulate in chondrocytes, which disturbs bone growth and leads to skeletal manifestations, such as skeletal dysplasia and a short stature. In addition, the disproportionate growth of the trachea can lead to airway insufficiency. We report the case of a 27-year-old man with dwarfism due to Morquio disease, which had resulted in quadriparesis, hyperreflexia, and dyspnea, requiring a "look up to the sky" compensatory position. Imaging studies of the neck showed tracheal tortuosity, spinal stenosis, myelopathy, and neurogenic arthropathy (Charcot joint). The patient was treated with occipital-cervical-thoracic instrumentation. However, postoperative tracheal correction was required. Considering the wide spectrum of clinical features in those with mucopolysaccharidosis type IVA, individualized multidisciplinary treatment is recommended.