CADASIL, a hereditary cerebral small vessel disease, is caused by mutations in the NOTCH3 gene. We analyzed 908 patients whose genetic testing was performed at Kyoto Prefectural University of Medicine (KPUM) from 1999 to March 2024, focusing on geographic area and the department requesting the genetic test. We found that the number of requests and positive results were influenced by geographic distance from KPUM. Most requests were from the Department of Neurology, whereas only 1.9% were from neurosurgery. Mutations of high frequency were identified in almost all areas in Japan. Mutations tended to more varied in Eastern than in Western Japan. To increase recognition of the diagnosis cases, it is important to increase awareness of the diagnosis by stroke specialists, in both neurology and neurosurgery.

We report a sibling case of progressive muscle weakness beginning in their 40s. The younger brother was initially suspected to have spinal muscular atrophy based on electromyography findings, but no SMN1 gene deletion was identified. Whole-exome sequencing in the siblings detected a heterozygous nonsynonymous mutation, c.577G>A (p.Ala193Thr), located in the actin-binding domain (ABD) of the filamin C (FLNC) gene. Muscle weakness of a sibling started in the proximal lower limbs and gradually progressed to the distal lower limbs, trunk, and upper limbs. Muscle MRI showed marked involvement of the medial and posterior thigh muscles, gastrocnemius, and soleus muscles, with relative sparing of the muscles of rectus femoris, gracilis, and tibialis anterior. These findings suggest a characteristic pattern of muscle involvement associated with this FLNC-ABD mutation.

We report a case of a woman diagnosed with neuronal intranuclear inclusion disease (NIID) 19 years after onset. The patient was 54 years old at onset and 73 years old at diagnosis. Various neurological symptoms, including hemianopia, ataxia, aphasia, and hemiparesis, persisted for several hours to several days. The patient continued to have loss of deep tendon reflexes and miosis. Brain MRI showed progressive deterioration of deep white matter lesions and brain atrophy, but diffusion-weighted imaging (DWI) showed no abnormalities. We experienced another patient with NIID with typical linear DWI hyperintensity at the corticomedullary junction, and the similarity of their clinical course (various neurological symptoms, including cortical signs, appearing and remitting within a short period of time) provided clues for the differential diagnosis of NIID. Skin biopsy and genetic testing were performed, and the diagnosis of NIID was confirmed. Some NIID patients lack typical DWI signs. It is important to raise NIID as a differential diagnosis when we see the patients with various neurological symptoms which is difficult to explain on monism.

Faciobrachial dystonic seizures are pathognomonic for leucine-rich glioma-inactivated 1 (LGI1) antibody-positive encephalitis, and can present as a faciobrachio-crural dystonic seizure (FBCDS) phenotype when the lower extremities are involved. A 77-year-old woman was admitted to our hospital with a 3-week history of recurrent falls. Sudden unilateral knee buckling due to FBCDS while standing led to falls, resulting in multiple contusions on her face and extremities. Brain MRI showed no abnormalities. Serum testing revealed positive LGI1 antibodies, confirming the diagnosis of LGI1 antibody-positive encephalitis. The symptoms resolved completely following combined treatment with immunotherapy and antiseizure medications. Clinicians need to recognize FBCDS as a rare but critical differential diagnosis in patients with repeated falls. Prompt identification of FBCDS and early treatment are essential to prevent serious injuries and progression of encephalitis.

Adult-onset Krabbe disease is a rare neurodegenerative disorder caused by mutations in the galactocerebrosidase (GALC) gene. It typically presents with slowly progressive central nervous system involvement, primarily characterized by pyramidal tract signs. We report the case of a 74-year-old man who presented with slowly progressive, asymmetric muscle atrophy associated with peripheral neuropathy, but without any clinical evidence of pyramidal tract involvement. Neurological examination revealed muscle wasting and weakness without spasticity or pathological reflexes. Based on the clinical presentation, differential diagnoses included motor neuron disease, Charcot–Marie–Tooth disease, and chronic inflammatory demyelinating polyneuropathy. Genetic analysis revealed a known pathogenic missense variant in the GALC gene: c.246A>G (p.I82M), confirming the diagnosis of Krabbe disease. These mutations have been previously reported in adult-onset Krabbe disease. This case lacked typical central nervous system signs and represents an atypical phenotype that may lead to delayed diagnosis. Our findings suggest that Krabbe disease should be considered in the differential diagnosis of adult patients presenting with unexplained neuropathy and marked muscle atrophy. Genetic testing plays a critical role in identifying such atypical cases, particularly when conventional diagnostic approaches fail to provide a definitive diagnosis.

A 69-year-old man developed generalized muscle spasms 9 days after undergoing surgery for a strangulated intestinal obstruction. He subsequently experienced respiratory failure and required mechanical ventilation in the intensive care unit. Tonic spasms were exacerbated by external stimuli, such as sound, and trismus emerged following tracheostomy. The patient was diagnosed as having tetanus, and targeted therapy was initiated, resulting in gradual clinical improvement. Tetanus is a neurotoxic syndrome caused by tetanospasmin, an exotoxin produced by Clostridium tetani, a bacterium commonly found in soil and present in human feces. Although rare, endogenous tetanus can occur following gastrointestinal surgery, likely due to translocation of the organism from the gut. This case highlights the need for clinicians to consider the gastrointestinal tract as a potential source of tetanus in postoperative patients presenting with muscle rigidity or spasms.