BACKGROUND: Pathogenic variants in Gap junction protein beta 1 (GJB1), which encodes Connexin 32, are known to cause X-linked Charcot-Marie-Tooth disease (CMTX), the second most common form of CMT. CMTX presents with the following five central nervous systems (CNS) phenotypes: subclinical electrophysiological abnormalities, mild fixed abnormalities on neurological examination and/or imaging, transient CNS dysfunction, cognitive impairment, and persistent CNS manifestations.
METHODS: A 40-year-old Japanese male showed CNS symptoms, including nystagmus, prominent spastic paraplegia, and mild cerebellar ataxia, accompanied by subclinical peripheral neuropathy. Brain magnetic resonance imaging revealed hyperintensities in diffusion-weighted images of the white matter, particularly along the pyramidal tract, which had persisted since childhood. Nerve conduction assessment showed a mild decrease in motor conduction velocity, and auditory brainstem responses beyond wave II were absent. Peripheral and central conduction times in somatosensory evoked potentials elicited by stimulation of the median nerve were prolonged. Genetic analysis identified a hemizygous GJB1 variant, NM_000166.6:c.520C > T p.Pro174Ser.
CONCLUSIONS: The patient in the case described here, with a GJB1 p.Pro174Ser variant, presented with a unique CNS-dominant phenotype, characterized by spastic paraplegia and persistent extensive leukoencephalopathy, rather than CMTX. Similar phenotypes have also been observed in patients with GJC2 and CLCN2 variants, likely because of the common function of these genes in regulating ion and water balance, which is essential for maintaining white matter function. CMTX should be considered within the spectrum of GJB1-related disorders, which can include patients with predominant CNS symptoms, some of which can potentially be classified as a new type of spastic paraplegia.

We present the case of a patient with leukoencephalopathy with calcifications and cysts (LCC), who experienced progressive severe hemiparesis despite multiple neurosurgical interventions of a large contralateral cyst. Bevacizumab was proposed as an ultimate treatment option based on prior case reports. While awaiting reimbursement approval for bevacizumab, major improvement occurred in both clinical and radiological disease manifestations. The disease course of LCC is variable and unpredictable; neurosurgical treatment should be reserved for severe and progressive neurological deficits. Bevacizumab has been reported as a promising alternative treatment option. Importantly, in our case the observed clinical improvement would have been attributed to the effects of bevacizumab, if started when requested. Our case underscores the need for a natural history study for LCC and the necessity of validating treatment efficacy by systematic evaluation through appropriate clinical trials rather than relying on anecdotal evidence from published case reports.

Labrune syndrome is a rare neurogenetic disorder with varied presentations. Here, we report the case of a 53-year-old male who presented with seizures, gait imbalance, and upper limb tremors for two years. Imaging studies revealed extensive leukodystrophy, multiple cerebral calcifications, and cystic lesions characteristic of Labrune syndrome. However, whole exome sequencing did not detect the SNORD118 mutation, typically associated with Labrune syndrome. Although the SNORD118 mutation is commonly found in Labrune syndrome, a few cases of the syndrome without this mutation have also been reported. This suggests the possibility that other yet undiscovered mutations may cause the same phenotype.

This is the case of a 26-year-old male who developed Anton Babinski syndrome (ABS), quadriplegia, and delayed post-hypoxic leukoencephalopathy (DPHL) after an opioid overdose. He exhibited cortical blindness, visual anosognosia, and confabulation upon awakening. Several days later, he experienced acute psychosis and agitation. T2-FSE MRI revealed extensive supratentorial leukoencephalopathy involving both cerebral hemispheres, extending to the posterior corpus callosum due to cerebral anoxia. This case report will discuss different types of encephalopathy from opioid abuse, ABS, visual anosognosia, and confabulation\'s pathogenic mechanisms. It underscores the necessity of researching substance-induced neuropsychiatric disorders and their pathogenic mechanisms for effective treatments.

Leukoencephalopathy (LE), characterized by structural changes affecting cerebral white matter, presents a complex clinical picture with diverse etiologies. This case report details the presentation, clinical findings, and physiotherapy management of a 32-year-old female with colony-stimulating factor 1 receptor (CSF1R)-related leukoencephalopathy and a history of diabetes and hypertension. She suddenly stopped her medications, which led to the worsening of her condition. She presented with symptoms of headache, slurred speech, visual disturbances, cognitive impairment, and impaired balance and coordination, due to which her activities of daily living were affected. The symptoms highlighted the challenges and multidisciplinary approach required for its management. The patient exhibited neurological deficits, cognitive decline, and abnormal reflexes, with magnetic resonance imaging (MRI) revealing white matter abnormalities. Outcome measures demonstrated significant improvements in cognitive and functional abilities, emphasizing the effectiveness of tailored rehabilitation in managing the complexities of colony-stimulating factor 1 receptor-related leukoencephalopathy. A six-week physiotherapy rehabilitation program addressed various domains, including strength training, task-specific exercises, errorless learning, facial muscle retraining, balance exercises, visual restoration therapy, and mobility training. All these interventions effectively improved her functional capacity and made the patient independent in performing activities of daily living.

Across the globe, snake envenomation causes significant morbidity and mortality. Although many clinical presentations and complications are observed in different types of snake bites, the incidence of leukoencephalopathy is rare. Although most cases of leukoencephalopathy are seen in viper bites, they are rarely seen in neurotoxic snake bites. In this report, we present a unique case of snake bite-induced leukoencephalopathy following a neurotoxic snake bite. The case highlights the importance of considering this rare complication in cases of snake bites presenting with neurological symptoms, particularly in those affecting higher mental functions.

OBJECTIVE: Primary angiitis of the central nervous system (PACNS) is a rare form of vasculitis solely affecting the vessels of the brain, spinal cord, and leptomeninges. A range of magnetic resonance imaging (MRI) features have been associated with PACNS, including cerebral infarction, hemorrhage, and parenchymal or leptomeningeal contrast enhancement.
RESULTS: We describe a 51-year-old man with a case of PACNS manifesting as akinetic mutism with progressive leukoencephalopathy.
CONCLUSIONS: Progressive leukoencephalopathy has not been well defined as a manifestation of PACNS. We review a small number of cases with comparable features, providing additional context on this PACNS manifestation with consideration of clinical subtypes.

Chemotherapy and radiotherapy are widely used in the treatment of central nervous system tumors and acute lymphocytic leukemia even in the pediatric population. However, such treatments run the risk of a broad spectrum of cognitive and neurological deficits. Even though the correlation with cognitive decline is still not clear, neuroradiological defects linked to white matter injury and vasculopathies may be identified. Thanks to the use of 7T MRI it is possible to better define the vascular pattern of the brain lesions with the added advantage of identifying their characteristics and anatomical localization, which, however, are not evident with a conventional brain scan. Moreover, the use of Quantitative Susceptibility Mapping (QSM) makes it possible to discriminate between calcium deposits on vessels (chemo-radiation-induced) and hemoglobin deposition in radio-induced cavernomas, speculating, as a result, about the pathophysiology of iatrogenic brain damage. We describe the case of a 9 year-old boy with a T-type acute lymphoid leukemia who had previously been treated with polychemotherapy and high-dose RT. To better define the child\'s neuroradiological pattern, 7T MRI and QSM were performed in addition to conventional imaging examinations. Our case report suggests the potential usefulness of a QSM study to distinguish radio-induced vascular malformations from mineralizing microangiopathy.

The opioid crisis has become a significant public health concern in recent years. Although respiratory depression and overdose are the most reported side effects of fentanyl, there have been rare cases of cerebellar leukoencephalopathy (CLE) following fentanyl intoxication. A 29-year-old man with a history of opioid use disorder and intravenous drug use presented to the emergency room with significant ataxia and dysarthria following fentanyl intoxication. According to the patient, the symptoms began four days prior after \"chasing the dragon\" with \"pure fentanyl\", and he reported experiencing nausea and dizziness, particularly during ambulation. Neurological examination revealed a positive Romberg test, ataxia, and delayed speech. Brain magnetic resonance imaging (MRI) indicated there was toxic degeneration of the cerebellar white matter that extended into the posterior limbs of the internal capsule. Urine drug screening was positive for opioids, making fentanyl-induced cerebellar leukoencephalopathy the most likely diagnosis in this case. This case of opioid-induced CLE underscores the critical significance of early recognition, which is vital for enhancing a patient\'s recovery and averting the development of severe neurological complications.

West Nile Virus, an arthropod-borne RNA virus, may result in severe neurological disease. West Nile neuroinvasive disease is characterized by meningitis, encephalitis, and possible acute flaccid paralysis. Classically, signal intensity abnormalities on T2-weighted magnetic resonance images are associated with poor outcomes. Herein, we present a case of previous West Nile encephalitis with diffuse leukoencephalopathy on imaging that demonstrates a favorable clinical outcome with limited neurologic sequelae. A 53-year-old male presented to the hospital with one month of headaches, dizziness, generalized weakness, and a seizure. His initial neurologic exam was notable for wide-based gait and imbalance. Magnetic resonance imaging (MRI) of the brain demonstrated diffuse bilateral white matter signal hyperintensities without contrast enhancement, suggestive of leukoencephalopathy. His lumbar puncture revealed lymphocytic pleocytosis and infectious studies demonstrated positive West Nile Virus immunoglobulin G (IgG) in the cerebrospinal fluid (CSF) and serum with negative immunoglobulin M (IgM) in both CSF and serum, suggestive of previous infection. A diagnosis of sequelae of West Nile neuroinvasive disease was made. He was started on anti-seizure medications without further seizures. At his subsequent nine-month follow-up visit, he remained asymptomatic without weakness, headaches, or confusion. Repeat MRI demonstrated interval improvement of white matter signal change. This case report highlights that West Nile neuroinvasive disease may present with profound white matter changes on MRI with limited clinical symptoms and long-term neurologic sequelae. Further research is needed to identify imaging correlation with symptom severity in this disease.