Teaching Video NeuroImages Research Articles

Teaching Video NeuroImages: A Triad of Tremor, Ataxia, and Cognitive Impairment

A 67-year-old woman presented with a 2-year history of forgetfulness and unsteadiness. She scored 17 on the Montreal Cognitive Assessment. She had tremor of head and upper limbs (video 1) since early adulthood, which was diagnosed as essential tremor. Brain MRI showed leukoencephalopathy and high signal intensity along the corticomedullary junction on diffusion-weighted images (figure 1). The diagnosis of adult-onset neuronal intranuclear inclusion disease (NIID) was confirmed by skin biopsy showing eosinophilic intranuclear inclusions (figure 2).1 NIID is a clinically heterogeneous rare neurodegenerative disease.2 Its characteristic MRI pattern should prompt confirmation of the diagnosis by skin biopsy.

Teaching Video NeuroImages: Marcus-Gunn pupil in tuberous sclerosis

A 22-year-old woman with tuberous sclerosis (TS) and an incomplete resection of a left-sided astrocytoma presented with a 4-year history of visual deterioration. Neurologic examination revealed a left relative afferent pupillary defect (RAPD) (video) with a pale left optic disc. Visual acuity was 20/100 bilaterally and a left-sided superior visual field loss was seen. Optical coherence tomography showed a left retinal hamartoma (figure 1). Contrast-enhanced brain MRI showed bilateral cortical and subcortical tubers (figure 2). Marcus-Gunn pupil or RAPD is a nonspecific feature denoting optic neuropathy.1 TS ophthalmopathy includes retinal and iris hamartomas, choroid colobomas, and hypopigmented lesions on iris and ciliary body.2

Teaching Video NeuroImages: Myoclonus as the presenting feature of Wilson disease

A 10-year-old boy with no pertinent medical or family history developed repeated falls and progressive gait and speech decline over 1 year. Examination revealed multifocal myoclonus and generalized dystonia (video). EEG lacked epileptiform activity. Kayser-Fleischer rings, serum ceruloplasmin of 6 mg/dL (normal 20–60 mg/dL), and 24-hour urinary copper of 108.94 μg (normal 15–60 μg) confirmed Wilson disease (WD). MRI brain revealed T2 and fluid-attenuated inversion recovery hyperintensity in basal ganglia, thalami, brainstem, and right frontal cortex, with the latter showing diffusion restriction (figure). The patient improved neurologically with zinc and penicillamine therapy. Myoclonus is uncommon in WD,1 with multifocal myoclonus at onset rarely reported.2

Teaching Video NeuroImages: Acquired focal neuromyotonia in LGI-1 autoimmunity

An 81-year-old woman was diagnosed with corticobasal degeneration (cognitive decline and left hand posturing). Hyponatremia and bilateral faciobrachial dystonic seizures (FBDS) ensued. Neurologic examination (figure, A; video) revealed persistent involuntary continuous left 3rd and 4th finger flexor activation and delayed relaxation. EMG revealed high-frequency spontaneous discharges, including neuromyotonia and fast myokymia of the left flexor digitorum superficialis and pronator teres (figure, B). LGI1 immunoglobulin G (IgG)1 was detected, but not CASPR2-IgG (figure, C–E). Oncologic evaluation revealed breast ductal carcinoma in situ. Encephalopathy and FBDS resolved after IV immunoglobulin. Encephalopathy coexisting with peripheral nerve hyperexcitability can mimic neurodegeneration, and should prompt exclusion of LGI1/CASPR2 autoimmunity.2

Teaching Video NeuroImages: A 20-year-old man with distal paresthesia

A 20-year-old man presented with a 3-week history of progressive distal paresthesia in his lower limbs. His gait became clumsy and he became unable to mobilize. The patient was vegetarian and after questioning admitted to regular recreational nitrous oxide use.

Teaching Video NeuroImages: Cold-induced laryngeal pseudomyotonia in Isaacs syndrome

A 36-year-old man developed progressive limb pain, excessive sweating, and muscle cramps. He described transient strained voice only after drinking cold water (video 1). Examination revealed generalized myokymia and pseudomyotonia. EMG revealed multiple spontaneous, continuous high frequency doublet and triplet motor unit discharges. Nerve conduction studies and chest CT scan were normal. CASPR2 and LGI1 antibodies were negative. Autoimmune, paraneoplastic, and other etiologies were excluded clinically as well as through additional serologic (or blood) testing and imaging. Symptoms resolved completely after IV immunoglobulin and carbamazepine for treatment of pain.

Teaching Video NeuroImages: Almost No Eye Movements to the Left

A 31-year-old patient had acute dizziness and lateropulsion to the right. Neuro-ophthalmologic examination revealed (1) a saccade and gaze palsy to the left (video 1, part A), (2) a “half-pathologic” head-impulse test to the right (video 1, part B), but (3) bilaterally normal adduction during convergence reaction (video 1, part C), findings typical for a left abducens nuclear palsy. It was caused by a histologically proven cavernoma in the tegmentum pontis (figure). To differentiate an abducens nuclear palsy from a combined lateral and contralateral medial rectus muscle palsy, one must test the convergence reaction, which goes via direct pathways to the oculomotor nucleus.1

Teaching Video NeuroImages: Susac syndrome's acute onset callosal disconnection

A 59-year-old right-handed hypertensive diabetic and previously alcoholic man presented acute confusional state followed by apathy, dysexecutive syndrome, clumsy left hand, and apraxic gait. A year later, his wife noticed impaired hearing. Neurologic examination revealed marked callosal apraxia (nondominant limb ideomotor apraxia, disconnection variant) and left stereoagnosis due to callosal disconnection (video). Left hand agraphia was present without aphasia. MRI showed punched out holes through corpus callosum, sparing the calloso-septal interface (figure 1). Audiometry revealed left neurosensorial loss. Fluorescein retinography demonstrated hyperfluorescence of arterial vessel wall (figure 2), confirming the hypothesis of Susac syndrome.1

Teaching Video Neuro Images : Shake Mom's hand to get the diagnosis

A term male newborn was admitted to the neonatal intensive care unit for respiratory distress and feeding difficulty. His 19-year-old mother was apparently healthy. The baby had generalized hypotonia, weakness, a weak cry, and a tented upper lip ([figure][1]). Maternal examination facilitated

Teaching Video NeuroImages: Facial myokymia and myorhythmia in anti-IgLON5 disease

A 79-year-old woman presented with an 8-month history of parasomnia and progressive bulbar syndrome with dysarthria, dysphagia, facial myokymia, and mandibular myorhythmia (video 1) resulting in biting scars of her lower lip. Brain MRI and EEG were unremarkable. CSF analysis showed intrathecal antibody synthesis and elevated tau 372 pg/mL (0–320 pg/mL) and phospho-tau 54 pg/mL (0–50 pg/mL). Antibodies against IgLON5 were highly positive (1:1,000) in CSF and serum. Anti-IgLON5 disease was diagnosed.1 Recognition of bulbar symptoms with myokymia and myorhythmia as part of an anti-IgLON5 disease may be important to start early immunotherapy to prevent progression to neurodegeneration.2

Teaching Video NeuroImages: A treatable rare cause of chorea

A 72-year-old woman developed progressive choreic movements involving the right hemibody and the orofacial muscles (video 1). Her examination was otherwise unremarkable, without ataxia. Brain MRI, blood glucose, thyroid function, and rheumatologic panel were unremarkable. Genetic testing for Huntington disease and C9orf72 expansions were negative. Initial hematocrit and hemoglobin levels were normal, but increased to abnormal values (56% and 18.5 g/dL) 1 year after chorea onset. The JAK2V617F mutation was positive, suggesting a diagnosis of chorea due to polycythemia vera. Chorea disappeared with phlebotomy and hydroxyurea. Neurologists should suspect this rare treatable entity in elderly patients with chorea even with initially normal hematocrit levels.1

Teaching NeuroImages and Teaching Video NeuroImages

The practice of neurology is rooted in a thorough medical history and comprehensive physical examination that form the bedrock of lesion localization. For many neurologists, the history they conduct and the examination they perform are an amalgamation of the techniques exemplified by their attending neurologists. Supplementing this bedside assessment is a broad range of electrophysiologic, radiographic, and other advanced imaging techniques that help the clinical practitioner make a neurologic diagnosis and devise an optimal treatment plan. The interpretation of abnormal examination findings, neuroimaging, and ancillary testing is a critical component of neurology training.

Author Response: Teaching Video NeuroImages: Pathologic Yawning: A Sign of Brainstem Involvement in Acute Disseminated Encephalomyelitis?

We thank Drs. Fujimori and Nakashima for their comment on our article.1 Their previously published report is certainly an interesting case as well.2 We agree that anti-myelin oligodendrocyte glycoprotein antibody testing is appropriate to include in cases of suspected acute disseminated encephalomyelitis (ADEM). We ordered a broad inflammatory and infectious workup for our patient on both serum and CSF, with the latter being repeated 5 days after initial presentation. Oligoclonal bands were noted in the CSF on 1 of 2 tests. The CSF IgG index was elevated (0.80 initially and 0.68 on follow-up; reference range 0.34–0.66). Anti-AQP4 antibodies were negative. Infectious workup showed negative serology for Epstein-Barr virus and cytomegalovirus. Viral PCR (including enterovirus) was negative, as was CSF mycobacterial culture. Mycoplasma pneumoniae IgM was positive in serum. Bartonella henselae serum IgG was also positive (1:640), but this was not believed to be clinically relevant. We ordered anti-MOG antibodies at the time of initial presentation, but unfortunately these were canceled by the laboratory because of a registration error; we have not reordered the test because the patient has completely recovered and the lesions seen on brain MRI have resolved. At this point, M. pneumoniae infection is the most likely trigger for the ADEM.

Reader Response: Teaching Video NeuroImages: Pathologic Yawning: A Sign of Brainstem Involvement in Acute Disseminated Encephalomyelitis?

With interest, we read the article by Birca et al.1 describing a 15-year-old adolescent boy with acute disseminated encephalomyelitis (ADEM) and a dorsal brainstem lesion who presented with pathologic yawning. We previously reported a 20-year-old man with antimyelin oligodendrocyte glycoprotein (MOG) antibody-associated brainstem encephalitis that involved the dorsal brainstem and cerebellum.2 Our case also presented with pathologic frequent yawning in addition to nystagmus, decreased hearing, and truncal ataxia on admission, although we did not describe these additional findings in detail in the article. Because it is well known that almost half of pediatric patients with ADEM are MOG-IgG seropositive3—and because MOG-IgG-associated brainstem encephalitis might relapse, as in our case—serum MOG-IgG status should be determined in this case as well.

Editors' Note: Teaching Video NeuroImages: Pathologic Yawning: A Sign of Brainstem Involvement in Acute Disseminated Encephalomyelitis?

Dr. Birca et al. reported a case of a 15-year-old adolescent boy who presented with acute-onset encephalopathy after a viral prodrome and was found to have frequent, dramatic yawning without electroencephalographic correlation and without focal deficits. The patient had elevated protein in the CSF without pleocytosis and bilateral brainstem, asymmetric insular, and cranial nerve T2 hyperintensities on brain MRI. He improved after treatment with methylprednisolone and was diagnosed with acute disseminated encephalomyelitis (ADEM). In response, Drs. Fujimori and Nakashima cite their previous report of a 20-year-old man with antimyelin oligodendrocyte glycoprotein (MOG) antibody-associated brainstem encephalitis who also presented with pathologic frequent yawning in addition to other brainstem symptoms. They suggest that serum MOG-immunoglobulin G (IgG) status should also be determined in the case by Dr. Birca et al., given that nearly half of pediatric patients with ADEM are MOG-IgG seropositive. Responding to these comments, senior author Dr. Myers agrees that anti-MOG-IgG testing is appropriate in cases of suspected ADEM and notes that a broad inflammatory and infectious workup was ordered on both serum and CSF for their patient, with lumbar puncture being repeated 5 days after initial presentation. Reviewing the results of CSF testing for their patient, Dr. Myers notes that there was an elevated IgG index, and oligoclonal bands on one sample, but whereas antiaquaporin-4 antibody testing was negative, they were unable to test for anti-MOG antibodies because of a laboratory registration error. As Mycoplasma pneumoniae immunoglobulin M was positive in the serum, mycoplasma infection was believed to be the most likely trigger for the patient's ADEM. This exchange highlights our evolving understanding of both the clinical manifestations and potential underlying etiologies of ADEM. Dr. Birca et al. reported a case of a 15-year-old adolescent boy who presented with acute-onset encephalopathy after a viral prodrome and was found to have frequent, dramatic yawning without electroencephalographic correlation and without focal deficits. The patient had elevated protein in the CSF without pleocytosis and bilateral brainstem, asymmetric insular, and cranial nerve T2 hyperintensities on brain MRI. He improved after treatment with methylprednisolone and was diagnosed with acute disseminated encephalomyelitis (ADEM). In response, Drs. Fujimori and Nakashima cite their previous report of a 20-year-old man with antimyelin oligodendrocyte glycoprotein (MOG) antibody-associated brainstem encephalitis who also presented with pathologic frequent yawning in addition to other brainstem symptoms. They suggest that serum MOG-immunoglobulin G (IgG) status should also be determined in the case by Dr. Birca et al., given that nearly half of pediatric patients with ADEM are MOG-IgG seropositive. Responding to these comments, senior author Dr. Myers agrees that anti-MOG-IgG testing is appropriate in cases of suspected ADEM and notes that a broad inflammatory and infectious workup was ordered on both serum and CSF for their patient, with lumbar puncture being repeated 5 days after initial presentation. Reviewing the results of CSF testing for their patient, Dr. Myers notes that there was an elevated IgG index, and oligoclonal bands on one sample, but whereas antiaquaporin-4 antibody testing was negative, they were unable to test for anti-MOG antibodies because of a laboratory registration error. As Mycoplasma pneumoniae immunoglobulin M was positive in the serum, mycoplasma infection was believed to be the most likely trigger for the patient's ADEM. This exchange highlights our evolving understanding of both the clinical manifestations and potential underlying etiologies of ADEM.

Teaching Video NeuroImages: Optic Ataxia as the Presenting Sign of the Heidenhain Variant of Creutzfeldt-Jakob Disease.

A 59-year-old woman presented with subacute onset of hand clumsiness followed by memory loss. She reported difficulty reaching for objects, although she could see them. Examination (video) showed optic ataxia, visual acuity of 20/30 OU, intact visual field, and near-normal finger-to-nose test. Hyperintense signals in the left temporo-parieto-occipital cortex in diffusion-weighted MRI, periodic triphasic complexes in EEG (figure), and elevated t-tau in CSF suggested the Heidenhain variant of Creutzfeldt-Jakob disease.1 The patient received supportive care and progressed to akinetic mutism. Optic ataxia—inaccuracy of visually guided arm movements—is a visuomotor disorder associated with lesions involving the posterior parietal cortex.2

Teaching Video NeuroImages: Wilson Disease Presenting With Catatonia.

A 29-year-old man with a history of depression on fluoxetine presented with 4 months of progressive abdominal pain and hypoactive encephalopathy. On examination, he was nonresponsive, bradykinetic, spastic, and had catatonia with waxy flexibility (video 1). Bush-Francis Catatonia Rating Scale score was 28 (table). He had new liver cirrhosis; serum ceruloplasmin was low and 24-hour urine copper was elevated. MRI revealed abnormal signal in basal ganglia and pons (figure). Two heterozygous mutations in the ATP7B gene (c.1934T > G and c.207 G > T) confirmed the diagnosis of Wilson disease. Zinc and penicillamine were initiated for copper reduction; catatonia did not respond to benzodiazepines. He was discharged home but required full care from family (nonambulatory, required help with all activities of daily living), and neurologic status was unchanged 3 months after discharge. Catatonia is a rare and underappreciated manifestation in Wilson disease1; early recognition is essential for prompt initiation of chelation therapy.2

Teaching Video NeuroImages: Multisystemic Erdheim-Chester Disease Presenting as a Cerebellar Ataxia.

A 41-year-old man was admitted to the neurology ward due to progressive vertigo and unsteadiness for the previous 2 months. Neurologic examination was remarkable for a global cerebellar syndrome. Investigation with brain MRI led to the hypothesis of a histiocytosis due to infiltrative lesions of the pons, cerebellar peduncles, and pituitary. Therefore, investigation progressed with chest/abdomen/pelvis CT, bone scintigraphy, and a tibial biopsy that confirmed the diagnosis of Erdheim-Chester disease (figures 1 and 2, video).

Teaching Video NeuroImages: A Triad of Tremor, Ataxia, and Cognitive Impairment

A 67-year-old woman presented with a 2-year history of forgetfulness and unsteadiness. She scored 17 on the Montreal Cognitive Assessment. She had tremor of head and upper limbs (video 1) since early adulthood, which was diagnosed as essential tremor. Brain MRI showed leukoencephalopathy and high signal intensity along the corticomedullary junction on diffusion-weighted images (figure 1). The diagnosis of adult-onset neuronal intranuclear inclusion disease (NIID) was confirmed by skin biopsy showing eosinophilic intranuclear inclusions (figure 2).1 NIID is a clinically heterogeneous rare neurodegenerative disease.2 Its characteristic MRI pattern should prompt confirmation of the diagnosis by skin biopsy.

Teaching Video NeuroImages: Spontaneous Third Ventriculostomy.

A 4-year-old boy with macrocephaly (+3 SD) was evaluated with MRI, which showed a subdural hygroma secondary to rupture of a left temporal arachnoid cyst and triventricular enlargement. Two years later, we repeated imaging to explore the possibility of a third ventriculostomy. There was a flow void across the floor of the third ventricle (figure). By using 3D cardiac-gated dynamic imaging, we demonstrated that a spontaneous ventriculostomy had already occurred (video, [links.lww.com/WNL/B217][1]). Spontaneous third ventriculostomy is rare and can occur in children and adults with chronic hydrocephalus.1 [1]: http://links.lww.com/WNL/B217