Confirming Pathogenicity of the F386L PSEN1 Variant in a South Asian Family With Early-Onset Alzheimer Disease

ObjectivesThe F386L PSEN1 variant has been reported in 1 Japanese family with limited clinical information. We aimed to prove that F386L is pathogenic by demonstrating that it segregates with early-onset Alzheimer disease (AD).MethodsEight individuals in a South Asian family provided DNA for genetic testing and underwent a neurologic examination.ResultsThe female proband was diagnosed with AD at age 45 years and died at age 49 years. She had a CSF biomarker profile consistent with AD, and her florbetaben PET scan was amyloid positive with high uptake in the striatum. Her MRI showed no prominent white matter disease. Her affected relatives had an age at onset range of 38–57 years and had imaging and biomarker profiles similar to hers.DiscussionThe results presented here, in conjunction with the prior report, confirm the pathogenicity of F386L. Furthermore, our study highlights the importance of studying families from underrepresented populations to identify or confirm the pathogenicity of rare variants that may be specific to certain genetic ancestries.

Continuous intraventricular vancomycin for treatment of ventriculitis using IRRAflow®: A case report

Background: Ventriculitis usually occurs as the result of infection and results in the inflammation of the ependymal lining of the ventricular system. Mortality rates remain high despite treatment. Case Description: We present the case of a 66-year-old man who presented with altered mental status and progressively became comatose. He was found to have fulminant ventriculitis due to a ruptured intracranial abscess. He was treated with bilateral IRRAflow® catheter (IRRAS, Stockholm, Sweden) placement through which continuous irrigation with vancomycin was initiated. Conclusion: This treatment was safe and led to improvement in the patient’s neurologic examination, imaging findings, and cerebrospinal fluid profiles.

The Outpatient Approach to Dizziness

The evaluation of the dizzy patient is complicated by many common pitfalls. The patient's description of symptoms and the standard neurologic examination are often nonspecific or unrevealing, and neuroimaging is most often normal. Over the past several years, research has demonstrated that a refocusing of history taking results in more reliable and diagnostically helpful information. This can guide a targeted expansion of the exam, often with an emphasis on eye movements.

Rapidly Progressive Gait and Coordination Difficulties

A 59-year-old woman noted sudden onset of slurred speech. Within a few days, she noted double vision, gait unsteadiness, and incoordination of her limbs. She sought care at her local emergency department. Computed tomography and magnetic resonance imaging of the head were negative for stroke. Her symptoms persisted. Neurologic examination indicated a moderate pancerebellar ataxia, without additional abnormalities. Her pursuit eye movements were saccadic. She had binocular diplopia with horizontal, gaze-evoked nystagmus. She had ataxic dysarthria and dysmetria of all limbs. Her steps and walking were irregular and she could not accomplish tandem gait. Additional neural antibody testing was undertaken, beyond the classic paraneoplastic antibodies. Metabotropic glutamate receptor 1-immunoglobulin G was detected in the serum and cerebrospinal fluid. The patient was diagnosed with autoimmune cerebellar ataxia. Because of the reported association of metabotropic glutamate receptor 1-immunoglobulin G with Hodgkin disease and non-Hodgkin lymphoma, positron emission tomography–computed tomography of the trunk (orbits to thighs) was performed, which was negative. After 6 weeks of intravenous methylprednisolone, the patient returned for evaluation. She had a mild ataxic dysarthria and minimal dysmetria of her left upper extremity only. She could tandem walk almost without error, and her gait appeared normal (no longer broad-based). At that point, immunotherapy was discontinued. At last follow-up, her neurologic examination findings remained stable. The subacute onset and rapid progression of ataxic symptoms in this adult patient led to suspicion for an autoimmune cause.

Orthostatism, Constipation, and Early Satiety

A 65-year-old woman with a history of Graves disease, status post radioactive iodine therapy, and a biopsy-proven benign calcified breast nodule sought care for evaluation of multiple symptoms. She had constipation for 8 years, with prior fecal urgency, and intermittent diarrhea for the previous year. She was diagnosed with irritable bowel syndrome. Her weight remained stable until 1 1/2 years earlier, and she had lost 6.8 kg. For the previous 3 years, the patient had experienced multiple urinary symptoms including hesitancy, urgency, incontinence, and retention. She was diagnosed with a cystocele, the correction of which did not help. She had noted difficulty focusing her eyes when moving from a dark to a well-lit environment, or vice versa. She also reported orthostatic light-headedness for 1½years, which worsened on exposure to a hot environment. Neurologic examination showed abnormally dilated pupils with prominently sluggish constriction in response to light. Autonomic reflex screening indicated patchy postganglionic sympathetic sudomotor, marked cardiovagal, and cardiovascular adrenergic failure, with neurogenic orthostatic hypotension. Thermoregulatory sweat testing showed 82% anhidrosis. A nuclear medicine gastric-emptying study indicated delayed gastric emptying and colonic hypomotility. Serum testing was markedly positive for ganglionic (alpha 3) acetylcholine receptor autoantibodies. The patient was diagnosed with autoimmune autonomic ganglionopathy. The patient received intravenous immunoglobulin. She returned and reported 80% improvement in all symptoms, and neurologic examination showed normal pupillary response to light. Autonomic reflex screening indicated improvement of her adrenergic function, and thermoregulatory sweat testing showed an impressive improvement of her sudomotor function. Her postganglionic sympathetic sudomotor and cardiovagal function remained impaired. Gastric emptying remained mildly delayed. She was maintained on intravenous immunoglobulin, which was later tapered after azathioprine was started. Autoimmune autonomic ganglionopathy usually presents subacutely, much like other autoimmune neurologic diseases. Typical features of this disorder are the impaired pupillary reaction to light and prominent sicca symptoms, indicating prominent cranial parasympathetic (cholinergic) impairment. Also consistent with this diagnosis are the prominent gastrointestinal tract symptoms. Prominent cholinergic failure helps distinguish autoimmune autonomic ganglionopathy from peripheral autonomic neuropathy or neurodegenerative disorders such as pure autonomic failure.

Progressive Myelopathy After Neck Pain

A 36-year-old woman with a history of hypothyroidism, gout, fibromyalgia, depression, substance use disorder, and nephrolithiasis had development of neck pain. Three months later, she noted numbness in the left leg, which slowly worsened over the course of several months, spreading to involve the right leg and eventually forming a sensory level across the trunk at T8. At that time she also noted numbness in both hands. She had stiffness and weakness in both legs and had trouble emptying her bladder. Neurologic examination showed mild weakness restricted to the bilateral iliopsoas and hyperreflexia in the upper and lower extremities. Hoffmann and Babinski signs were positive bilaterally. There was moderate spasticity in both lower extremities and mild distal vibratory sensation loss, with a sensory level across the trunk at T8. Her gait examination indicated a spastic gait, and she had a mildly positive Romberg sign. On re-evaluation of her previous magnetic resonance image, a transverse band or pancakelike enhancement pattern was noted at the center of a moderate to severely stenotic region of the cervical spine sparing gray matter on axial sequences. The magnetic resonance imaging findings were highly suggestive of cervical spondylotic myelopathy. A neurosurgical referral was made, and the patient underwent anterior cervical discectomy with decompression and fusion from C4-C7. At her follow-up visit 4 months after surgery, the patient reported improvement in her strength and walking. Her neurologic examination showed normal lower extremity strength, resolution of spasticity, and negative Babinski sign bilaterally but persistent sensory deficits. Magnetic resonance imaging of the cervical spine at that time showed a decrease in the degree of T2 hyperintensity and enhancement, consistent with interval response to surgery. The presence of a progressive myelopathy over many months in this case patient argued against a diagnosis of transverse myelitis. Furthermore, the cerebrospinal fluid was noninflammatory, which also favored cervical spondylosis over idiopathic transverse myelitis. However, the gadolinium enhancement pattern was the key diagnostic feature that strongly suggested cervical spondylotic myelopathy as the diagnosis and ultimately led to neurosurgical referral for decompression.

Peripheral Nerve Disorders

Disorders of the peripheral nerves are some of the most common conditions that neurologists face in clinical practice. The wide differential diagnosis that often accompanies peripheral nerve disorders may be narrowed by careful attention to the history (time course, severity, preexisting disease, and family history); peripheral neuroanatomy; patient symptomatology (sensory loss, paresthesia, pain, and weakness); and neurologic examination (sensory loss, weakness, atrophy, and reduced muscle stretch reflexes). Electromyography is used to assess large-diameter myelinated axons (touch, pressure, vibration, proprioception, and motor) and aid in localization by helping to narrow the differential diagnosis and predict axonal or demyelinating pathophysiology.

Relationship between admission vitals and brain herniation in 32 cats: a retrospective study

Objectives The aim of the study was to evaluate whether any admission vitals correlated with the presence of brain herniation diagnosed via MRI in cats presenting with neurologic signs. Methods Medical records at two veterinary university referral centers were reviewed to identify cats that underwent brain MRI between 2010 and 2019. A control group of cats with intracranial lesions without concurrent brain herniation was analyzed for comparison. Data relating to signalment, vitals on admission, abnormalities observed on initial neurologic examination, underlying etiology, advanced imaging findings and outcome were reviewed. A Modified Glasgow Coma Scale (MGCS) score was determined retrospectively based on initial neurologic examination. Logistic regressions were performed to investigate the relationship between each risk factor and the odds of brain herniation as diagnosed on MRI. Results Thirty-two cats with brain herniation and 44 cats with abnormal brain MRI without evidence of herniation (as a control group) based on MRI findings were included. Cats with intracranial neoplasia vs other diagnoses were found to be at increased risk of herniation (odds ratio [OR] 4.8, 95% confidence interval [CI] 1.8–13.8; P = 0.001). The odds of herniation increased with age (OR 1.1, 95% CI 1.01–1.2; P = 0.031). Cats with herniation had a significantly lower level of consciousness in their MGCS score ( P <0.0001) than cats without herniation. There was no significant difference in either motor activity or brainstem reflexes between the groups ( P >0.05). Conclusions and relevance Admission heart rate and blood pressure were not associated with brain herniation. Cats with herniation were presented with a significantly lower level of consciousness in their MGCS score; however, this clinical feature cannot be directly attributable to and predictive of herniation. Older cats with intracranial neoplasia are more likely to have brain herniation.

Case Report: Suspected Solitary Osseous Plasmacytoma in a Cat: Use of Magnetic Resonance Imaging to Diagnose and Confirm Resolution of Disease Following Chemotherapy

A 9-year-old female spayed Domestic Shorthair cat presented for pain, reluctance to jump, and hyporexia of 14 days duration. Neurologic examination was consistent with C6-T2 myelopathy. Magnetic resonance imaging (MRI) revealed a solitary, contrast-enhancing lesion within the T2 vertebral body. Solitary osseous plasmacytoma was diagnosed based on neurologic examination, advanced imaging, and clinicopathologic findings. Melphalan and prednisolone therapy were initiated. Complete resolution of clinical signs and the vertebral lesion were documented at a 2-year follow up examination with neurologic examination and repeat spinal MRI, respectively. Solitary osseous plasmacytoma are rare neoplasms in humans and domestic animals. As such, there is a paucity of published information regarding diagnostic criteria, MRI findings, treatment modalities, progression, and remission of disease in the feline patient. Most data are extrapolated from human medicine. The purpose of this report is to document neurologic exam and MR findings at the time of diagnosis and complete resolution of a solitary osseous vertebral plasmacytoma following melphalan and prednisolone therapy.