A Case of Thyrotoxic Periodic Paralysis: "I Can't Move!"

Thyrotoxic periodic paralysis (TPP) is a form of hypokalemic periodic paralysis associated with hyperthyroidism. It is characterized by hypokalemia associated with acute proximal symmetrical lower limb weakness and can progress to involve all four limbs and the respiratory musculature. We present a case of a 27-year-old Asian male with recurrent attacks of weakness in all four extremities. A subsequent diagnosis of thyrotoxic periodic paralysis was made, which was secondary to a previously undiagnosed Grave's disease. TPP should be a differential in a young male of Asian ethnicity who presents to the hospital with acute onset of paralysis.

An Unusual Case of Giant Cell Arteritis.

Giant cell arteritis (GCA), also known as temporal arteritis (TA), is a systemic autoimmune inflammation of medium and large arteries. It is the most common vasculitis affecting adults older than 50, with an incidence of 20/100,000 and an average age of onset of 70. Typically, patients initially present with new-onset headaches, visual changes and disturbances, jaw claudication, arthralgias, and tender or swollen temporal or occipital arteries. Our patient is a 73-year-old male who presented to the emergency room with 10 days of bilateral headache radiating to the occipital area associated with fevers, persistent chills, generalized weakness, and a headache described as constant, dull, 9 out of 10 pain, and minor pain with neck flexion. Lab work revealed an elevated erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP). The patient had tender palpation to his temples and due to a high suspicion of giant cell arteritis, he was started on high-dose steroids with rapid relief of his symptoms. Biopsy showed evidence of active non-granulomatous vasculitis and confirmed bilateral temporal arteritis within the context of the clinical setting. GCA patients are more likely to be women and typically present with unilateral headache (66% of GCA), jaw claudication (50%), fevers (50%), and transient visual loss (16-54%). Here, we describe a 73-year-old male with a past medical history of cerebral vascular accident (CVA), diabetes, and cancer that presented with 10 days of bilateral headaches and fevers. Unlike the usual presentation, our patient denied any vision and joint pain changes, and the temporal arteries were not stiff to palpation. This patient presentation is unique to previous reports in the limited display of symptoms and absence of the most commonly associated manifestations. Although his presentation supported GCA, the features of elevated ESR and CRP, headache, and fever were too general to diagnose GCA exclusively, and his additional symptoms of rhinorrhea and sinus pain more likely supported infection. Our case indicates the importance of maintaining a high index of clinical suspicion for GCA in the elderly population presenting with headaches and elevated ESR and CRP. GCA, also known as temporal arteritis (TA), is a systemic autoimmune inflammation of medium and large arteries. Typically, patients initially present with new-onset headaches, visual changes and disturbances, jaw claudication, arthralgias, and tender or swollen temporal or occipital arteries. Diagnosis requires high clinical suspicion, and treatment revolves around high doses of steroids.

Neuronal vulnerability and multilineage diversity in multiple sclerosis.

Multiple sclerosis (MS) is a neuroinflammatory disease with a relapsing-remitting disease course at early stages, distinct lesion characteristics in cortical grey versus subcortical white matter and neurodegeneration at chronic stages. Here we used single-nucleus RNA sequencing to assess changes in expression in multiple cell lineages in MS lesions and validated the results using multiplex in situ hybridization. We found selective vulnerability and loss of excitatory CUX2-expressing projection neurons in upper-cortical layers underlying meningeal inflammation; such MS neuron populations exhibited upregulation of stress pathway genes and long non-coding RNAs. Signatures of stressed oligodendrocytes, reactive astrocytes and activated microglia mapped most strongly to the rim of MS plaques. Notably, single-nucleus RNA sequencing identified phagocytosing microglia and/or macrophages by their ingestion and perinuclear import of myelin transcripts, confirmed by functional mouse and human culture assays. Our findings indicate lineage- and region-specific transcriptomic changes associated with selective cortical neuron damage and glial activation contributing to progression of MS lesions.

Single-cell genomics identifies cell type-specific molecular changes in autism.

Despite the clinical and genetic heterogeneity of autism, bulk gene expression studies show that changes in the neocortex of autism patients converge on common genes and pathways. However, direct assessment of specific cell types in the brain affected by autism has not been feasible until recently. We used single-nucleus RNA sequencing of cortical tissue from patients with autism to identify autism-associated transcriptomic changes in specific cell types. We found that synaptic signaling of upper-layer excitatory neurons and the molecular state of microglia are preferentially affected in autism. Moreover, our results show that dysregulation of specific groups of genes in cortico-cortical projection neurons correlates with clinical severity of autism. These findings suggest that molecular changes in upper-layer cortical circuits are linked to behavioral manifestations of autism.