Rhythmic Jaw Movements in Amyotrophic Lateral Sclerosis: Is It Clonus or Tremor?

Background: Jaw clonus refers to involuntary, rhythmic jaw contractions induced by a hyperactive trigeminal nerve stretch reflex; however, the movements, when triggered without a stretch, can be confused with a tremor. Phenomenology Shown: This video demonstrates a patient with amyotrophic lateral sclerosis presenting with rapid rhythmic jaw movements seen at rest, alongside a power spectrum analysis revealing a narrow high-frequency peak of 10 Hz. Educational Value: Rhythmic jaw movements are seen in many disorders such as Parkinson's disease, essential tremor, tardive syndromes, and cranial myorhythmias; however, a high-frequency movement, regardless of clonus or tremor, can indicate amyotrophic lateral sclerosis when accompanied by typical upper and lower motor neuron signs. Highlights: The presented video abstract shows a patient with amyotrophic lateral sclerosis with rhythmic jaw movements seen at rest. A power spectrum analysis of the rhythmic movements revealed a 10 Hz peak, a frequency higher than those seen in patients with Parkinson's disease, essential tremor, myorhythmia, and tardive syndromes.

Serotonin Syndrome: An Emerging Reality in the Emergency Department.

Serotonin syndrome (SS) is an entity caused by interference with the serotonin metabolism and/or by medications that act as serotonin receptor agonists. The signs and symptoms are nonspecific, making the diagnosis challenging. Treatment depends on the severity of the manifestations. In mild to moderate cases, it typically resolves within the first 24 hours after initiating therapy and discontinuation of the serotoninergic medications. A 42-year-old woman with a previous history of depression was admitted to the hospital due to the voluntary ingestion of multiple tablets of escitalopram 10 mg and venlafaxine 75 mg. Physical examination showed a hyperthermic and diaphoretic patient. Tremor, agitation, bilateral ocular clonus, and spontaneous inferior limb clonus were also present. Hunter's criteria were applied, and the diagnosis of SS was assumed. Supportive and symptomatic treatments were initiated. The evolution was benign, with symptomatic remission in the first 24 hours. In the last decades, a large increase in the use of antidepressants was noted, and, as such, defining SS as rare is no longer appropriate. Delaying the treatment can dictate an increase in morbidity and mortality. It is important to highlight that the diagnosis is mainly clinical as diagnostic criteria may miss out on some cases. As such, clinical awareness of SS's multiplicity of presentations is of utmost importance.

Ethylmalonic encephalopathy masquerading as meningococcemia.

Ethylmalonic encephalopathy (MIM #602473) is a rare autosomal recessive metabolic condition caused by biallelic variants in ETHE1 (MIM #608451), characterized by global developmental delay, infantile hypotonia, seizures, and microvascular damage. The microvascular changes result in a pattern of relapsing spontaneous diffuse petechiae and purpura, positional acrocyanosis, and pedal edema, hemorrhagic suffusions of mucous membranes, and chronic diarrhea. Here, we describe an instructive case in which ethylmalonic encephalopathy masqueraded as meningococcal septicemia and shock. Ultrarapid whole-genome testing (time to result 60 h) and prompt biochemical analysis facilitated accurate diagnosis and counseling with rapid implementation of precision treatment for the metabolic crisis related to this condition. This case provides a timely reminder to consider rare genetic diagnoses when atypical features of more common conditions are present, with an early referral to ensure prompt biochemical and genomic diagnosis.

On saline infusion, clonus, molecules and forgotten scientists: Who was Dr Julius Sander (1840-1909)?

Zitterbewegungen des Fusses bei Dorsalflexion (shaking movements of the foot upon dorsal flexion) were observed independently from each other and described in the same issue of a German peer reviewed journal by Carl Westphal (1833-1890) at the Charité in Berlin and by Wilhelm Erb (1840-1921) in Heidelberg. While Westphal used the term Fussphaenomen, Erb is credited with coining the term clonus for the phenomenon. Both scientists are immortalized by various eponyms acknowledging their respective contributions to science. Little is known however about Julius Sander (1840-1909), in those days resident at Charité, who noticed the phenomenon and presented it to his superiors, Wilhelm Griesinger (1817 -1868) and Westphal. In addition to such observations, Sander made original contributions in resuscitation physiology while working with Hugo Kronecker (1839-1914). With Kronecker, Sander published observations on life saving transfusions with inorganic salt solutions in dogs "Bemerkung über lebensrettende Transfusion mit anorganischer Salzlösung bei Hunden" a very early work on isovolemic fluid resuscitation. The purpose of this communication is to highlight Sander's scientific contributions and to shed some light on his life, of which a German Lexicon stated that after 1870 no information on him can be ascertained anymore.

Chronic serotonin syndrome: A retrospective study.

BACKGROUND: Serotonin syndrome (SS) is an underdiagnosed drug-induced clinical syndrome resulting from the excess intrasynaptic concentration of serotonin. Very limited information is available about chronic SS. AIM: To evaluate the epidemiological, clinical, and other aspects of the insidious onset SS. METHODS: We retrospectively evaluated 14 consecutive adult patients (> 18 years) who had complaints for more than 6 wk at the time of consultation and met the Hunter criteria for SS. RESULTS: The mean age was 41.1 years (range: 21-61 years), with a male preponderance (64%). Although tremors were observed in all patients, this was a presenting complaint in only 43% of patients. Generalized body pain, insomnia, and restlessness were common presenting features (50% each). Other common clinical features were stiffness of the limbs (43%), diaphoresis (43%), gait disturbances (36%), bowel disturbances (36%), dizziness (29%), sexual dysfunctions (21%), incoordination (14%), and fatigue (14%) The mean duration of symptoms before the diagnosis of SS was 13.5 ± 5.8 wk (range: 6-24 wk). Amitriptyline was the most common drug (n = 6, 43%), followed by tramadol (n = 5, 36%) and sodium valproate (n = 5, 36%). All patients received cyproheptadine, a 5- hydroxytryptamine2A antagonist, as treatment and noted an excellent response over the course of 4-14 d. CONCLUSION: This study represents the largest study on chronic SS. We suggest that patients receiving serotonergic drugs should be physically examined for the presence of SS upon the development of new symptoms.

A movement disorder specialist gets a taste of his own medicine.

We present a case in which a movement disorder neurologist developed two different hyperkinetic movements due to corticospinal tract hyperexcitability, which resolved completely with surgical removal of an epidural spinal canal tumor. The first-hand description of these movements creates a unique opportunity for enhanced insight into these complex movement phenomena.

Jaw Clonus: A Rhythmic Oscillatory Movement, but Not Tremor.

Background: Jaw clonus is rhythmic, oscillatory contraction of jaw muscles induced by stretch and is caused by lesions of the descending motor neurons in the corticopontine tracts. Phenomenology shown: We illustrate jaw clonus elicited with jaw activation and upon testing of the jaw jerk in a patient with amyotrophic lateral sclerosis. Educational value: This video clearly demonstrates the uncommon sign of jaw clonus, a finding which needs to be distinguished from tremor and should direct the examiner to consider lesions of the corticopontine fibres, including amyotrophic lateral sclerosis.

Pediatric Emergency Medicine Didactics and Simulation (PEMDAS): Serotonin Syndrome.

Introduction: Serotonin syndrome is caused by an accumulation of serotonin in the body from drug interactions or overdose of serotonergic medications, including commonly used antidepressants. Symptoms can be life-threatening and encompass both neurologic and cardiovascular toxicity, including agitation, seizure, tachycardia, rhabdomyolysis, and hyperthermia. Methods: This simulation case was developed for pediatric emergency medicine fellows and emergency medicine residents in the pediatric emergency department and can be altered to accommodate other learners. The case involved a 16-year-old male, represented by a low- or high-fidelity manikin, who presented with altered mental status/agitation after an overdose of antidepressant medication. The team of learners was required to perform a primary and a secondary assessment; manage airway, breathing, and circulation; and recognize and initiate treatment for serotonin syndrome. The patient had a seizure resulting in airway compromise requiring advanced airway support, as well as developed rhabdomyolysis requiring aggressive fluid hydration. We created a debriefing guide and a participant evaluation form. Results: Fifty-seven participants across five institutions completed this simulation, which included residents, fellows, faculty, and students. The scenario was rated by participants using a 5-point Likert scale and was generally well received. Participants rated the simulation case as effective in learning how to both recognize (M = 4.9) and manage (M = 4.8) serotonin syndrome. Discussion: This pediatric emergency simulation scenario can be tailored for a range of learner backgrounds and simulation environments. We used the participant evaluation form to improve future iterations of the simulation.

Jaw clonus in neuromyelitis optica spectrum disorder with subsequent osmotic demyelination syndrome.

Jaw clonus, a fascinating, yet uncommon clinical sign, is suggestive of supranuclear lesions of the trigeminal nerve. It has previously been reported in association with amyotrophic lateral sclerosis. Hereby, we report an index case of jaw clonus in a patient of neuromyelitis optica spectrum disorder with subsequent osmotic demyelination syndrome with pseudobulbar palsy due to the involvement of pontine corticobulbar fibres.

Disrupted Ankle Control and Spasticity in Persons With Spinal Cord Injury: The Association Between Neurophysiologic Measures and Function. A Scoping Review.

Control of muscles about the ankle joint is an important component of locomotion and balance that is negatively impacted by spinal cord injury (SCI). Volitional control of the ankle dorsiflexors (DF) is impaired by damage to pathways descending from supraspinal centers. Concurrently, spasticity arising from disrupted organization of spinal reflex circuits, further erodes control. The association between neurophysiological changes (corticospinal and spinal) with volitional ankle control (VAC) and spasticity remains unclear. The goal of this scoping review was to synthesize what is known about how changes in corticospinal transmission and spinal reflex excitability contribute to disrupted ankle control after SCI. We followed published guidelines for conducting a scoping review, appraising studies that contained a measure of corticospinal transmission and/or spinal reflex excitability paired with a measure of VAC and/or spasticity. We examined studies for evidence of a relationship between neurophysiological measures (either corticospinal tract transmission or spinal reflex excitability) with VAC and/or spasticity. Of 1,538 records identified, 17 studies were included in the review. Ten of 17 studies investigated spinal reflex excitability, while 7/17 assessed corticospinal tract transmission. Four of the 10 spinal reflex studies examined VAC, while 9/10 examined ankle spasticity. The corticospinal tract transmission studies examined only VAC. While current evidence suggests there is a relationship between neurophysiological measures and ankle function after SCI, more studies are needed. Understanding the relationship between neurophysiology and ankle function is important for advancing therapeutic outcomes after SCI. Future studies to capture an array of corticospinal, spinal, and functional measures are warranted.

Atypical Cauda Equina Syndrome with Lower Limb Clonus: A Literature Review and Case Report.

BACKGROUND: Cauda equina syndrome (CES) is a neurosurgical emergency warranting urgent surgical decompression. Treatment delay may precipitate permanent adverse neurological sequelae. CES is a clinical diagnosis, corroborated by radiological findings. Atypical presentations should be acknowledged to avoid inappropriately rejected diagnoses. CASE DESCRIPTION: We report the case of a woman exhibiting bilateral lower limb weakness, perineal numbness, sphincter disturbance, and lower limb clonus. Classically, CES displays lower motor neuron signs in the lower limbs. The presence of clonus, an upper motor neuron sign, brought the diagnosis into doubt. The history included chronic fatigue, difficulty mobilizing, and intermittent blurred vision. A lumbosacral magnetic resonance imaging (MRI) scan demonstrated a large disc prolapse at L5/S1. The cord was not low-lying or tethered. Therefore, the possibility of second diagnoses, including of inflammatory or demyelinating nature, was raised. An urgent MRI scan of the brain and cervicothoracic cord identified no other lesions. On balance, the clinical presentation could overwhelmingly be attributed to the L5/S1 disc prolapse. Given the time-critical nature of cauda equina (CE) compression, an urgent laminectomy and discectomy was offered with continued postoperative investigation of the clonus. Intraoperatively, significant CE compression was found. The operation proceeded uneventfully and the patient recovered fully. In the immediate postoperative period, the clonus persisted yet subsequently resolved completely. CONCLUSIONS: We conclude that the clonus was attributable to CE compression and not a second pathology. The corresponding neuroanatomical correlate remains nondelineated. The presence of clonus does not preclude a diagnosis of CES. If the clinicoradiological information otherwise correlate, surgery should not be delayed while alternative diagnoses are sought. The literature is also reviewed.

Síndrome opsoclonus-mioclonus-ataxia asociado con un teratoma ovárico maduro en un paciente pediátrico / Opsoclonus-mioclonus-ataxia syndrome associated with a mature ovarian teratoma in a pediatric patient

Resumen El síndrome de opsoclonus-mioclonus-ataxia es una entidad rara que cursa con síntomas motores, neurocognitivos y psiquiátricos, con frecuencia marcadamente debilitantes. El síndrome se reporta con mayor frecuencia en adultos que en niños, la etiología es variada, pero en pediatría se presenta en la mayoría de los casos como un síndrome paraneoplásico. En este contexto la neoplasia más frecuentemente asociada es el neuroblastoma. La evidencia actual apoya la tesis de que este es un síndrome mediado inmunológicamente al haberse identificado una serie de auto-anticuerpos en los pacientes afectados, y a que muchos de ellos responden a terapia inmunosupresora. La importancia del reconocimiento de este síndrome radica en que existe tratamiento médico y quirúrgico que podría mejorar el pronóstico neurológico y psiquiátrico. Presentamos el caso de una paciente que se presentó con este síndrome en nuestra institución.

Abstract The opsoclonus-myoclonus-ataxia syndrome is a rare entity that presents with motor, neurocognitive and psychiatric symptoms, often markedly de bilitating. The syndrome is reported more frequently in adults than in chil dren, the etiology is varied, but in pediatrics it occurs in most cases as a paraneoplastic syndrome. In this context, the most frequently associated neoplasm is neuroblastoma followed by gynecological tumors. The current evidence supports the thesis that this is an immune-mediated syndrome because a series of circulating autoantibodies has been described in the affected patients, in addition to many of them responding to immuno suppressive therapy. The importance of recognizing this syndrome is that there is medical/surgical treatment available that could improve the neu rological and psychiatric prognosis. Next, we present the case of a patient who presented with this syndrome in our institution.

Defining the spectrum of spasticity-associated involuntary movements.

BACKGROUND: Spasticity can be associated with several hyperkinetic involuntary movements generally referred to as "spasms" despite different phenomenology and clinical characteristics. OBJECTIVE: To better characterize the phenomenology and clinical characteristics of spasticity-associated involuntary movements. METHODS: We performed a cross-sectional study of a consecutive patient sample from the spasticity clinic. Each patient was interviewed by a movement-disorder neurologist who conducted a standardized movement-disorder survey and a focused exam. Patients with involuntary movements were video-recorded and videos were independently rated by a separate blinded movement-disorder neurologist. RESULTS: Sixty-one patients were included (54% female, mean age 49.7 ± 13.9 years). Of the entire cohort, 11.5% had spinal, 44.3% had cerebral, and 44.3% had mixed-origin spasticity. Fifty-eight patients (95%) reported one or more involuntary movements: 75% tonic spasms (63% extensor, 58% isometric, 41% flexor/adductor), 52% spontaneous clonus, 34% myoclonus, 33% focal dystonia, and 28% action tremor. One third of the involuntary movements were painful. Only 53% of patients reported that their involuntary movements were much or very-much improved with their current anti-spasticity management. Patients treated with intrathecal baclofen therapy were more likely to report much or very-much improvement compared to patients receiving oral and/or botulinum therapy (P = 0.0061 and 0.0069 respectively). CONCLUSION: Most spastic patients experience spasticity-associated involuntary movements of variable phenomenology and impact. However, only half of these patients experience significant improvement with the current management strategies. More research is needed to explore better treatment options for spasticity-associated involuntary movements with focus on phenomenology-specific approaches.

Early α-linolenic acid exposure to embryo reduces pentylenetetrazol-induced seizures in zebrafish larva.

Over the past few years, there has been a tremendous increase in interest of general population toward food-based therapies for management of chronic clinical conditions due to their lesser adverse effects with prolonged use over pharmacotherapies. Foods enriched with omega-3 fatty acids have shown some promising results in case of epilepsy. The present study was envisioned to investigate the effect of early exposure of α-linolenic acid (ALA), an essential omega-3 fatty acid in developing zebrafish (Danio rerio) embryos toward pentylenetetrazol (PTZ)-induced seizure susceptibility. The healthy wild-type zebrafish embryos were incubated in system water or system water containing different ALA concentrations (1-20 µM) till 7 dpf (days post fertilization). Each larva at 7 dpf was placed in 8 mM PTZ solution and seizure event was recorded. ALA incubation at 10 µM and 20 µM concentrations showed a dose-dependent reduction in PTZ-mediated hyperactive responses in larvae indicated by a marked decrease in total distance travelled and speed, as compared to vehicle control. Furthermore, both the treated groups showed increase in the latency to PTZ-induced clonus-like seizures in larvae, as compared to vehicle control. ALA incubated larvae at 10 µM and 20 µM concentrations also showed a significant reduction in c-fos mRNA level. A marked increase in the level of ALA and docosahexaenoic acid was also observed in the larvae incubated at highest effective concentration of ALA. The present study concluded that embryonic exposure of ALA reduced PTZ-induced seizures in zebrafish larva.

Serotonin Syndrome in the Emergency Department.

With the widespread use of serotonergic agents including many antidepressants, antiemetics, illicit drugs, and even some herbal supplements, serotonin syndrome is a condition seen more frequently. It can appear abruptly and, if untreated, can progress to a life-threatening state. Prompt recognition and treatment is imperative to avoid complications. The presentation is variable and can be confused with other conditions. The authors present a case of serotonin syndrome that was recognized early and treated promptly in the emergency department.

An unusual case of infective pneumocephalus: case report of pneumocephalus exacerbated by continuous positive airway pressure.

BACKGROUND: Pneumocephalus, illustrated by air in the cranial vault is relatively infrequent and generally associated with neurosurgery, trauma, meningitis and barotrauma. However cases of spontaneous non-traumatic pneumocephalus remain rare. While the relationship between continuous positive airway pressure (CPAP) and atraumatic pneumocephalus has been previously reported, to our knowledge the rare presentation associated with sinus wall osteomyelitis has never been described. We summarize here the case of a 67-year-old woman's acute presentation of Streptococcus salvarius infection after a sudden drop in her consciousness. CASE PRESENTATION: The patient was brought to hospital by family reporting a one week history of sudden deterioration, cognitive decline, and lethargy. The patient presented with reduced arousal, cognitive function (Glasgow Coma Scale: 10, Abbreviated Mental Test Score:CS, 0 AMTS), and no history of trauma. Computed Tomography (CT) imaging was ordered and identified a significant pneumocephalus with no cranial defect. Further investigations acknowledged possible sinus or middle ear disease, which was highlighted by the discovery of S. salivarius by polymerase chain reaction (PCR) and potentially exacerbated by the use of nocturnal continuous positive airway pressure (CPAP). The patient made a complete recovery by eliminating likely causative factors and long term regimental antibiotics administration. CONCLUSION: This case highlights a rare neurological presentation of S. salivarius infection with a mixed aetiology of spontaneous pneumocephalus. This case features an atypical complication associated with CPAP use, and to our knowledge is the first case to be associated with sinus wall osteomyelitis. Recognition of the clinical features and risk factors for spontaneous pneumocephalus -while rare-serve to broaden our clinical index of suspicion when presented with patients experiencing neurological deficit. Information from this case may also aid in improving prevention, early diagnosis, and future management.

Effect of Botulinum Toxin on Clonus: A Systematic Review.

OBJECTIVE: To conduct a systematic review of the literature that examined the effect of botulinum toxin type A on clonus. DATA SOURCES: A literature search of multiple databases (PubMed, Cochrane, Google Scholar, Embase) was performed to identify articles published in English in the past 30 years (1986-2016). STUDY SELECTION: Two reviewers independently applied the following inclusion criteria: (1) any adult patients older than 18 years with upper motor lesion; (2) any location and duration of clonus; and (3) subjective and objective measurements of clonus tested at least 2 weeks after botulinum toxin injection. DATA EXTRACTION: Two reviewers independently extracted the data and assessed the methodological quality. A consensus method was used to solve disagreements. DATA SYNTHESIS: The systematic review resulted in 164 articles, of which 14 met the inclusion criteria: 3 were randomized controlled trials, 1 was nonrandomized, and 6 were case series and 3 case studies. All studies (181 patients) showed improvement in clonus: 6 of 14 results were statistically significant. Different scales were used for clonus measurement, such as clonus score, patient diaries, clonus spasm score, and electromyogram duration. CONCLUSIONS: Overall, there was preliminary evidence indicating improvement in clonus after botulinum injection. The major drawback with studies reviewed here was a large variation in the type of clonus assessment tools, which also lacked validity, reliability, and sensitivity to small changes in clonus.

Serotonin syndrome presenting as febrile encephalopathy with CSF pleocytosis: a report of three cases.

Serotonin syndrome (SS) is an iatrogenic, drug-induced clinical syndrome caused by serotoninergic hyperstimulation. SS may have protean manifestations and can mimic a variety of medical conditions. Herein, we describe three cases of febrile encephalopathy who were on serotonergic agents. All three cases fulfilled Hunter's criteria for SS and responded to the removal of the offending agents and the administration of cyproheptadine. All three patients had abnormal cerebrospinal fluid (CSF) examinations (pleocytosis in three patients and increased protein in two patients) which returned to normal with therapy. We suggest that SS presenting as febrile encephalopathy may have transient CSF abnormalities. Severe SS is a medical emergency. Therefore, a trial of cyproheptadine can be given in patients fulfilling the SS criteria even in the presence of CSF abnormalities. In parallel, the patients should be investigated for other causes of febrile encephalopathy and CSF pleocytosis.