eNeurologicalScieNeurologicalSci Vol 19

June 2020

Review Article

Measuring upper limb function in MS: Which existing patient reported outcomes are fit for purpose?

James Close, Kathryn Baines, Laurie Burke, Jeremy Hobart

  • Article 100237
  • https://doi.org/10.1016/j.ensci.2020.100237
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  • Abstract

    Multiple Sclerosis (MS) clinical trials increasingly focus on progressive and advanced MS, with upper limb function (ULF) as a key outcome. Within clinical trials, Patient Reported Outcomes (PROs) quantify clinical variables and establish meaningfulness of changes. Scientific standards and regulatory criteria (from Food and Drug Administration [FDA]) require PROs be "fit-for-purpose": well-defined and reliable measures of specific concepts in defined contexts.

    This review article is to identify, from literature, existing PROs measuring ULF and determine which satisfy scientific and regulatory clinical trials requirements.


Original Articles

Comparison of pseudocontinuous arterial spin labeling perfusion MR images and time-of-flight MR angiography in the detection of periictal hyperperfusion

Noritoshi Shirozu, Takato Morioka, So Tokunaga, Takafumi Shimogawa, ... Koji Iihara

  • Article 100233
  • https://doi.org/10.1016/j.ensci.2020.100233
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  • Abstract

    Magnetic resonance imaging (MRI), including perfusion MRI with three-dimensional pseudocontinuous arterial spin labeling (ASL) and diffusion-weighted imaging (DWI), are applied in the periictal (including ictal and postictal) detection of circulatory and metabolic consequences associated with epilepsy. Our previous report revealed that periictal hyperperfusion can firstly be detected on ASL, and cortical hyperintensity of cytotoxic edema secondarily obtained on DWI from an epileptically activated cortex. Although magnetic resonance angiography (MRA) using three-dimensional time-of-flight is widely used to evaluate arterial circulation, few MRA studies have investigated the detection of periictal hyperperfusion.

Monoamine oxidase B rs1799836 G allele polymorphism is a risk factor for early development of levodopa-induced dyskinesia in Parkinson's disease

Shoko Kakinuma, Minako Beppu, Setsu Sawai, Akitoshi Nakayama, ... Tomoaki Tanaka

Dopamine replacement therapy is an established treatment for motor symptoms of Parkinson's disease, but its long-term use is often limited by the eventual development of motor complications, including levodopa-induced dyskinesia. Genetic background, particularly polymorphisms of dopamine metabolism genes, may affect the occurrence of dyskinesia in Parkinson's disease patients.

Prevalence of the major neurological disorders in a semi-urban community in northern Benin

Thierry Adoukonou, Laurine Adogblé, Mendinatou Agbétou, Dieu donné Gnonlonfoun, ... Edgard-Marius Ouendo

  • Article 100242
  • https://doi.org/10.1016/j.ensci.2020.100242
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  • Abstract

    Neurological disorders are some of the most disabling diseases. Epidemiological data on their incidence in Benin are scarce.

    The prevalence of major neurological diseases among people older than 15 years was investigated in Titirou through a cross-sectional study and door-to-door survey which took place from June 10 to August 30, 2014, in the district of Titirou and included 1094 persons.


Case Reports

Cerebral venous congestion correlates to acute aneurysm rupture: An illustrative case with Doppler ultrasonography study

Virginia Annese, Claudia Frau, Noemi Murdeu, Massimo Gregorio, Sandro Sanguigni

  • Article 100231
  • https://doi.org/10.1016/j.ensci.2020.100231
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  • Abstract

    The objective of our description is to shed light on some new hemodynamic and clinical characteristics in the unstable cerebral aneurysm Case: We describe a 54 year old woman who presented a tension headache, that increasing for several days. A CT scan performed in ER suggests a possible arterial ectasia at the level of the circle of Willis. The patient is hospitalized. An angio CT shows an aneurysm of the anterior communicating artery, without signs of fixation and/or other instability. A subsequent TCCD examination with venous study shows clear congestion at the level of the spheno-parietal sinus. The Valsalva maneuver determines an increase in local congestion. In the light of the ultrasound picture, the patient was quickly received in Neurosurgery with success.

    We describe a clinical case where the worsening tension headache was not secondary to the increase of volume of the aneurysm but was an epiphenomenon of venous congestion, explored with TCCD.

Neuroimaging of septo-optic dysplasia-plus with midbrain hypoplasia and ophthalmoplegia

Colin Y. Wang, Daniel T. Ginat

  • Article 100235
  • https://doi.org/10.1016/j.ensci.2020.100235
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  • Abstract

    Septo-optic dysplasia is a rare brain malformation that can be associated with anomalous cortical development, such as schizencephaly, which is referred to as septo-optic dysplasia plus. This report describes septo-optic dysplasia-plus associated with unilateral atrophy of the midbrain and oculomotor nerve deficiency, which was diagnosed on MRI in a teenage male who presented with ophthalmoplegia.

Pembrolizumab treatment of metastatic urothelial cancer without exacerbating myasthenia gravis

Akiko Ishii, Minato Yokoyama, Hiroshi Tsuji, Yasuhisa Fujii, Akira Tamaoka

  • Article 100236
  • https://doi.org/10.1016/j.ensci.2020.100236
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  • Abstract

    Pembrolizumab is an immune checkpoint inhibitor (ICI) that targets the programmed cell death (PD)-1 receptor. It significantly increases the overall survival in patients with locally advanced or metastatic urothelial cancer. However, its administration may induce serious immune-related adverse effects, such as myocarditis and myasthenia gravis (MG). Therefore, ICI treatment may have been withheld for MG patients with cancer. We report the first case in which pembrolizumab was used safely without aggravation of MG symptoms in right renal pelvic and bladder cancers, even though the anti-acetylcholine receptor antibody (anti-ACh-R Ab) serum concentration increased. The patient was a 70-year-old man diagnosed with stage III renal pelvic cancer and bladder cancer, with multiple liver metastases. He was previously diagnosed with MG at the age of 58 years. During second-line treatment with pembrolizumab, his anti-AChR Ab levels increased from 0.8 to 10.9, without exacerbation of MG symptoms. The liver metastases disappeared after five courses of pembrolizumab. This report shows that MG is not a reason to refrain from using PD-1 inhibitors in cancer patients; it should be considered when treatment is performed in highly experienced centers.

A novel mutation in the GBA2 gene in a Japanese patient with SPG46: A case report

Keiko Nakamura-Shindo, Kenjiro Ono, Kishin Koh, Hiroyuki Ishiura, ... Masahito Yamada

  • Article 100238
  • https://doi.org/10.1016/j.ensci.2020.100238
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  • Abstract

    Hereditary spastic paraplegia (HSP) is a neurodegenerative disorder characterized by pyramidal weakness and spasticity of the lower limbs. SPG46, one of autosomal recessive HSP, is clinically characterized by spasticity and pyramidal weakness of the lower limbs, mental retardation, congenital bilateral cataract, thin corpus callosum, and hypogonadism in males. Mutations in the nonlysosomal glucosylceramidase β2 (GBA2) gene have been identified in patients with SPG46. A Japanese woman was identified with bilateral cataracts when she was in an elementary school. She felt falling easily, speaking unclearness, and difficulty in walking and raising her left leg in her 30s. Her neurological examination at the age of 44 revealed dysarthria, spasticity in the upper and lower extremities, increased jaw jerk and tendon reflexes in the extremities, bilateral extensor plantar reflexes, ataxia, and pollakiuria. Magnetic resonance imaging showed thinning of the corpus callosum body as well as atrophy in the pons and cerebellum. A novel homozygous c.1838A > G (p.D613G) missense mutation was detected at exon 12 in GBA2. We diagnosed her illness as an autosomal-recessive form of hereditary SPG46. The clinical features matched previously reported phenotype of SPG46. This is the first report of a Japanese patient with SPG46 with a novel mutation in GBA2. We presume that the novel GBA2 missense mutation found in our patient would cause loss of GBA2 activity, resulting in the neurological manifestations of SPG46.

Differential diagnosis of HaNDL syndrome in a case report of a pediatric patient: The role of SPECT with 99mTc-HMPAO

Paula Fernández-Rodríguez, José Antonio Lojo-Ramírez, Manuel Medina Rodríguez, José Manuel Jiménez-Hoyuela García, David García-Solís

Logopenic aphasia due to Lewy body disease dramatically improved with donepezil

Kazuo Kakinuma, Toru Baba, Michinori Ezura, Keiko Endo, ... Kyoko Suzuki

Four cases of progressive multifocal leukoencephalopathy in iatrogenic immunocompromised patients

Alessia Bianchi, Paolo Ragonese, Maria Aurelia Banco, Sabrina Realmuto, ... Giuseppe Salemi

  • Article 100243
  • https://doi.org/10.1016/j.ensci.2020.100243
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  • Abstract

    Progressive multifocal leukoencephalopathy (PML) is a demyelinating disease of the central nervous system (CNS) caused by John Cunningham Virus (JCV). We report four PML cases in immunocompromised patients, respectively treated with (1) Natalizumab, (2) Rituximab, (3) autologous stem-cell transplantation, and (4) Tacrolimus. All patients underwent neurological examination, magnetic resonance imaging (MRI), magnetic resonance spectroscopy (MRS), JCV-DNA research on biological samples, and lymphocytes subpopulation study. All cases presented with motor, behavioural, and cognitive disorders. Visual, sensitive, and cerebellar deficits developed in three cases. MRI revealed widespread progressive demyelinating areas with active borders; three patients presented contrast enhancement. One patient developed inflammatory reconstitution syndrome (IRIS). At MRS, all cases presented decreased N-acetyl-aspartate (NAA) and three cases showed increased choline (Cho). In one patient, plasma and urine tested positive for JCV-DNA, while cerebrospinal fluid (CSF) analysis confirmed JCV in two patients. The fourth patient had a low JCV-DNA blood titer and brain biopsy showed subacute necrosis. Two patients had abnormal lymphocyte subpopulations. Three patients underwent therapy with Mirtazapine, one of whom received Mefloquine in add-on. No clinical response was registered. Clinical onset, MRI and MRS were highly suggestive of PML in all patients, despite three cases presented contrast enhancement. In three cases JCV-DNA detection in biological samples confirmed the diagnosis. The fourth patient fulfilled diagnosis of "presumptive PML". Our data confirm the importance to complete the diagnostic workup despite the presence of findings not completely consistent with classical PML. We hypothesize that atypical characteristics could due to the clinical conditions leading to PML.


Letters to the Editor

Cerebellar stroke-like lesions in Leigh syndrome may mimic cerebellar cortical bleeding

Josef Finsterer