Clinical Neurology最新文献

Amyotrophic lateral sclerosis (ALS) is an intractable motor neuron disease characterized by progressive degeneration of motor neurons with varying degrees of frontotemporal lobe dysfunction. This English summary of the addendum to the Japanese clinical practice guidelines for ALS outlines major recent advances in pharmacological therapy in Japan. Following the development of the 2023 guidelines, three additional medications-oral edaravone, high-dose intramuscular mecobalamin, and tofersen-have been introduced. Oral edaravone, with its ease of administration, demonstrates pharmacokinetics comparable to the intravenous formulation. High-dose mecobalamin reduces functional decline when initiated early in the disease course. Tofersen, an antisense oligonucleotide, is the first gene-targeted therapy approved in Japan for patients with copper/zinc superoxide dismutase gene-related ALS, highlighting the importance of genetic testing and counseling in all ALS cases. This addendum provides updated expert consensus recommendations for the use, dosing, and monitoring of these therapies, while emphasizing the need for thorough communication about the ethical and psychological dimensions of genetic testing. It also addresses practical considerations for combination therapy, noting that up to three or four anti-ALS agents are now available in Japan. The long-term safety and efficacy of these therapies, as well as their potential synergistic or additive effects, remain to be clarified through real-world data and prospective registries. The objectives of this addendum are twofold: to present these advances and recommendations in English to foster international collaboration, and to inform the global ALS community about the latest therapeutic strategies in Japan. In addition, ongoing efforts to harmonize clinical evaluation standards and promote international clinical trials are highlighted, with the goal of improving patient outcomes and advancing ALS research worldwide.

The patient was a male in his 50s. He had been aware of headache since the end of April, X year, and was admitted to the Neurosurgery Department of X Hospital in early May; however, his headache and posterior neck pain worsened. He was discharged from the previous hospital and admitted to this hospital in late May. His consciousness was clear, and there were no abnormalities in his cranial nerves or limb motor systems. Tendon reflexes were normal and Babinski's sign was negative. He complained of posterior neck pain and remained in bed all day with his neck flexed backward. Head MRI showed a high fluid-attenuated inversion recovery (FLAIR) signal, high diffusion-weighted imaging (DWI) signal, and low T₂* signal around the inferior horn of left lateral ventricle, and contrast-enhanced MRI showed a diffuse contrast effect on the cerebral surface, brainstem, and spinal cord soft membrane. Cerebrospinal fluid (CSF) analysis showed 98 cells/μl (66% mononuclear cells, 34% polymorphonuclear cells), protein level of 140 ‍mg/dl, and glucose level of 32 ‍mg/dl (simultaneous blood glucose 160 ‍mg/dl); cytology was negative. Malignant lymphoma, fungal/tuberculous meningitis, meningeal carcinomatosis, and granulomatous disease were suspected; however, no abnormalities were observed. In mid-June, the patient's condition suddenly deteriorated, and he died. Autopsy revealed an epithelioid glioblastoma (isocitrate dehydrogenase [IDH]-wild-type, World Health Organization [WHO] grade IV) near the left subventricular angle, with diffuse infiltration of the glioblastoma on the cerebral surface, brainstem, and spinal cord pia mater. The patient was diagnosed with glioblastoma with diffuse leptomeningeal spread.

The case involves a 60-year-old female with a history of more than five years of treatment with a thrombopoietin receptor agonist (TPO-RA) for idiopathic thrombocytopenic purpura (ITP). She presented to our hospital with complaints of headache and left hemiparesis. Diffusion-weighted MRI of the head showed mild hyperintensity from the right thalamus to the basal ganglia, suggesting edematous changes. The patient was diagnosed with cerebral venous sinus thrombosis caused by thrombocytopenia induced by TPO-RA therapy. It is necessary to consider that there is a risk of thrombosis not only in the early stages after starting TPO-RA therapy but also in cases such as this one, even after a long period of time.

A 51-year-old woman presented with left drop foot at age 20, numbness in the right fourth and fifth fingers at age 45, and numbness in both lower extremities at age 51. Lumbar MRI revealed multiple cauda equina nodules, while ultrasonography of the peripheral nerve identified enlarged nerve bundles in several locations, including the right ulnar and left peroneal nerves. Nerve conduction studies and upper extremity MRI findings were consistent with these observations, and head MRI confirmed the absence of auditory schwannomas. Schwannomatosis (SWN) is a rare disease characterized by the formation of multiple peripheral schwannomas, associated with genetic abnormalities such as SMARCB1 and LZTR1. When multiple peripheral nerve tumors are detected, SWN should be considered as part of the differential diagnosis.

Perioperative complications of MR-guided focused ultrasound therapy for Vim-targeted tremor are often reported, such as weakness and paresthesia. In this paper, five cases of dysgeusia after MR-guided focused ultrasound therapy targeting the Vim in patients with essential tremor are presented. All patients also suffered from sensory disturbances. In most cases, dysgeusia is mild, but there have been reports of patients with severe weight loss. Dysgeusia has also been reported in deep brain stimulation therapy. Dysgeusia is a complication that should be considered in the treatment of Vim-targeted tremor. Our own cases of taste disorder are reported, along with a review of the literature.

A 74-year-old man sustained a left femoral neck fracture following a fall on day X. Approximately four hours after the injury, he developed impaired consciousness, which persisted even after osteosynthesis was performed on day X+1. Brain MRI on day X+2 revealed multiple hyperintense lesions scattered in the bilateral cerebral hemispheres on diffusion-weighted imaging (DWI), leading to a diagnosis of cerebral fat embolism (CFE). Despite treatment with methylprednisolone and protirelin, his condition did not improve. Nonconvulsive status epilepticus was treated with levetiracetam; however, consciousness remained impaired. Serial brain MRI revealed progressive confluence of white matter lesions. Hyperintense areas on DWI in the cerebral white matter persisted into the subacute and chronic phases. Together with previous reports, this case highlights the potential association between persistence of DWI hyperintensity approximately one month after onset and poor neurological outcomes in patients with CFE.

A 57-year-old man was rushed to our hospital with acute right hemiplegia. Head MRI revealed high signals in the left motor cortex that did not correspond to vascular control, mainly in the cortex, on DWI. However, serum and cerebrospinal fluid were positive for syphilis antibodies, cerebrospinal fluid protein was elevated, and there was no atrial fibrillation. Head MRA and MRV were normal, so the patient was diagnosed with neurosyphilis and antisyphilis therapy was administered. However, the right hemiplegia did not improve much, so an additional steroid was administered, which resulted in a marked improvement in clinical symptoms. It is thought that the steroid contributed to the improvement of symptoms in this case due to vasculitis caused by Treponema pallidum, an excessive immunological response to the destruction of the bacteria, and cytokine release due to inflammation. Additional administration of steroids may be considered in addition to antisyphilis therapy.

A 67-year-old woman undergoing chemoradiotherapy for breast cancer had fever and impaired consciousness. Brain MRI showed abnormal signals in the bilateral frontal lobes. The patient was diagnosed with a brain abscess. The abnormal signal in the right frontal lobe decreased in size with antibiotic treatment, but the abnormal signal in the left frontal lobe worsened. Cytomegalovirus (CMV) was detected in the cerebrospinal fluid. Following administration of ganciclovir, the abnormal signal in the left frontal lobe decreased in size and consciousness improved. Based on the clinical course, we diagnosed a coexisting brain abscess and CMV encephalitis. However, the patient died of respiratory failure caused due to progression of breast cancer and underwent an autopsy. Pathological findings suggested different etiologies for the left and right frontal lobes. They supported the clinical diagnosis of coexisting brain abscess and cytomegalovirus encephalitis. This case indicated that in immunosuppressed patients, coexisting CMV infection and bacterial infection should be considered.