Introduction {#s1}
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Neurotoxoplasmosis can induce a wide variety of movement disorders including myoclonic jerks especially in immunodeficient individuals.[@b01] We report a case illustrating sleep-related, multifocal, myoclonic jerks in neurotoxoplasmosis in an immunocompetent adult that responded adequately to treatment.

Toxoplasmosis is also a ubiquitous infectious illness, which has been considered a global threat. Neurotoxoplasmosis is additionally being increasingly recognized as a cause of cryptogenic epilepsy and this case provides further credence to this hypothesis.[@b01]

By this report, we highlight myoclonus as a manifestation of neurotoxoplasmosis even in the apparently immunocompetent patient, thereby promoting earlier and widespread recognition and consequently appropriate treatment.

Case report {#s2}
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We describe a case of multifocal, myoclonic jerking during sleep ([Video 1](#v01){ref-type="other"}) in encephalitis as a result of neurotoxoplasmosis in a 39-year-old immunocompetent adult male who had daily contact with 20 resident cats for 2 years. The patient presented to hospital with a flu-like syndrome for 3 days and with multifocal, sleep-related, myoclonic jerks for 1 day. These movements consisted of abnormal, sudden, isolated, brief, small-amplitude, multifocal muscle jerks involving various body areas, in particular the patient's head, right upper limb, fingers, and legs. The phenomenon was observed only during sleep without causing incontinence or arousal and its occurrence was not noted during wakefulness. The myoclonus would start in the first hour of sleep and remained unchanged throughout sleep during the day or at night. We found a pattern of three to five sequences of muscle contractions per minute, each lasting 2--3 minutes followed by a period of a non-observable phenomena of 20--30 minutes' duration. These movements occurred four to six times daily for 7 days. The patient was always unaware of those events that subsided spontaneously without benzodiazepines ([Video 1](#v01){ref-type="other"}). There was no clinical evidence of other sleep disturbances such as obstructive sleep apnea, sleep-related hypoxemia (saturation of oxygen was 100% on room air), hypoventilation syndromes, narcolepsy, or insomnia.

###### Demonstration of Myoclonic Jerks in our Patient. This video shows multifocal, myoclonic jerks of the patient's head, right upper limb, fingers, and legs. These involuntary intermittent jerky movements took place during the day or night but only during sleep without causing incontinence or arousal. We found an observable pattern of three to five sequences of muscle contractions per minute, each lasting 2--3 minutes followed by a period of non- observable phenomena of 20--30 minutes' duration. These movements occurred four to six times daily for 7 days. Myoclonus was not observed after spontaneous arousal or while the patient was awake. The patient was always unaware of those events that subsided spontaneously without benzodiazepines.

There was no history of previous illness, surgery, exposure to chemicals, use of recreational drugs, consumption of alcohol, or recent travel abroad. He was febrile (38.8°C), tachycardic (110 beats/minute) with blood pressure of 145/82 mmHg and a respiratory rate of 20 breaths per minute, and he had 100% oxygen saturation on room air. Two, non-tender, soft lymph nodes, 1.2 cm in diameter, were palpable in the cervical region.

There was leukocytosis (13.8 × 10^9^/L) with eosinophilia (14.1%) and elevated C-reactive protein at 31.1 mg/dL. Immunoglobulin (Ig) G antibodies to *Toxoplasma gondii* were detected in the serum and cerebrospinal fluid (CSF) with an elevated titer of 198 and 20 IU/mL respectively by using an electro-chemiluminescence immunoassay. Serum and CSF IgM antibodies to *T. gondii* were also positive. The CSF contained 47 cells/mm^3^ and 0.8 g/L protein, both being elevated values. An enzyme-linked immunosorbent assay for human immunodeficiency virus infection (HIV) was non-reactive in serum and polymerase chain reaction testing was unavailable. Magnetic resonance imaging of the brain and spinal cord and scalp electroencephalography (EEG) were normal. The patient had an excellent outcome after specific treatment for toxoplasmosis (trimethoprim--sulfamethoxazole) and the myoclonic jerking disappeared completely in 7 days. The investigations and treatment of the patient are illustrated in [Tables 1](#t01){ref-type="table"} and [2](#t02){ref-type="table"}. He remained healthy at the 1-year follow-up.

Table 1Medical InvestigationsTests Performed on AdmissionResultReference Range**Blood test**WBCs13.8 × 10^9^/L4.5--11.0 × 10^9^/LEosinophils14.1%0.0--0.6%Hemoglobin15.2 g/dL14.0--17.5 g/dLMean corpuscular volume83.2 fL/red cell80--96 fL/red cellPlatelet count350 × 10^3^/µL156--373 × 10^3^/µLSerum potassium4.1 mmol/L3.5--5.1 mmol/LSerum sodium138 mmol/L135--145 mmol/LSerum creatinine0.8 mg/dL0.5--1.2 mg/dLBUN11 mg/dL3--20 mg/dLUric acid4.5 mg/dL2.5--8 mg/dLAlanine aminotransferase60 IU/L20--60 IU/LAspartase aminotransferase40 IU/L5--40 IU/LGamma glutamyl transpeptidase60 U/L8--61 IU/LLactate dehydrogenase330 IU/L105--333 IU/LAlkaline phosphatase129 U/L40--129 IU/LAlbumin4.9 g/dL3.5--5.5 g/dLAlbumin-corrected calcium9.6 mg/dL9.6--11.2 mg/dLCRP31.1 mg/dL0.0--1.0 mg/dLFasting blood sugar80 mg/dL60--120 mg/dLVDRL testNon-reactiveNon-reactive or reactiveFTA-ABSNegativePositive or negativeElisa for HIVNon-reactiveNon-reactive or reactiveAntistreptolysin O titer90 IU/mL0--200 IU/mL*Toxoplasma gondii* IgG antibodies198 IU/mLPositive: greater than 1.09 IU/mL*Toxoplasma gondii* IgM antibodiesPositivePositive or negative*Toxoplasma gondii* specific IgG avidityHigh avidity (AI \> 50%)Low avidity (AI ≤ 50%)High avidity (AI \> 50%)Herpes virus 1 IgG antibodiesLess than 0.9Index negative: Less than 0.9Herpes virus 1 IgM antibodiesLess than 0.9Index negative: less than 0.9Herpes virus 2 IgG antibodiesLess than 0.9Index negative: Less than 0.9Herpes virus 2 IgM antibodiesLess than 0.9Index negative: less than 0.9CMV IgG antibodies0.800 UA/mLNegative: less than 1.5 UA/mLCMV IgM antibodies0.778 UA/mLNegative: less than 1.1 UA/mLEBV IgG antibodies3.3Positive: Greater than 22EBV IgM antibodies0.1Negative: less than 0.8Hepatitis BsAGNegativePositive or negativeHepatitis C IgG antibodiesNegativePositive or negativeHepatitis C IgM antibodiesNegativePositive or negative*Echinococcus granulosus* IgG antibodyNegativePositive or negativeAnti-double stranded DNANegativePositive or negativeAntinuclear antibodyNegativePositive or negativePerinuclear antineutrophil cytoplasmic antibodies5.42 U/mLNegative: less than 10.0 U/mLCytoplasmic antineutrophil cytoplasmic antibodies3.73 U/mLNegative: Less than 10.0 U/mLPCR for viral infections or toxoplasmosisTests not obtainedNegative or positive**Other investigations**Mantoux testNegativePositive or negativeElectrocardiogramSinus tachycardiaNormal or abnormalChest X-rayNormalNormal or abnormalEchocardiogramNormal ejection fraction 75%Normal or abnormalCT scan of the brain with contrastNormalNormal or abnormalMRI/MRA scans of the brainNormalNormal or abnormalCSF analysisCSF opening pressure was 14 cm of H~2~O. CSF contained 47 cells/mm^3^, 0.8 g/L of proteins, and the glucose concentration was 60 mg/dL. CSF culture showed no bacterial growth and cytology was negative for neoplastic cells. VDRL was non-reactive and India ink test for *Cryptococcus neoformans* was negative*Toxoplasma* gondii IgG antibodies in CSF20 IU/mLPositive: greater than 1.09 IU/mL*Toxoplasma gondii* IgM antibodies in CSFPositivePositive or negative**Tests performed in the follow-up blood test***Toxoplasma gondii* IgG antibodies20 IU/mLPositive: greater than 1.09 IU/mL*Toxoplasma gondii* IgM antibodiesPositivePositive or negativePCR for viral infections or toxoplasmosisTests not obtainedNegative or positive**Other investigations**Scalp EEGNormalNormal or abnormalEMG and nerve conduction studiesNormalNormal or abnormalPCR for viral infections or toxoplasmosis in CSFTests not obtainedNegative or positiveVideo-EEG, polysomnography and jerk locked backed averaging studiesTests not obtainedNormal or abnormal[^1]

Table 2Medical TreatmentDosagePeriod of Treatment**Intravenous therapy initiated on admission day**Trimethoprim--sulfamethoxazole160 mg/800 mg 3 times daily2 weeksNormal saline isotonic solution1 L daily1 weekPantoprazole40 mg twice daily3 days**Oral drugs initiated on admission day**Carbamazepine200 mg 2 times daily6 daysParacetamol1 g three times daily7 days**Other oral drugs**Trimethoprim--sulfamethoxazole80 mg/400 mg per tablet 2 tablets 2 times daily4 weeks initiated on day 15Pantoprazole40 mg once daily14 days initiated on day 4

Discussion {#s3}
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Central nervous system (CNS) toxoplasmosis can cause multiple movement disorders and seizures including multifocal myoclonic jerks, even with normal EEG and magnetic resonance imaging/magnetic resonance angiography scans of the brain.[@b01]--[@b03]

Myoclonic jerks because of neurotoxoplasmosis in immunocompetent individuals are rare and we found no other similar reports in the literature. Recent studies have also implicated chronic or latent toxoplasmosis as a possible cause of cryptogenic seizures and/or epilepsy in the immunocompetent individual, which gives added relevance to this case.[@b01] We suggest that mild clinical expression of disease and normal imaging studies in this case were due to immunocompetence in the patient.

Atypical toxoplasmosis encephalitis with limited clinical expression and with normal conventional imaging may also demonstrate multifocal myoclonic jerking in an immunocompetent host and be due to atypical genotypes of *T. gondii.* Reinfection with toxoplasmosis has been reported among immunocompetent human hosts. Reinfection with toxoplasmosis can occur among people chronically and with heavy exposure to *T. gondii* such as in our patient. Owing to the severity of encephalitis caused by these atypical genotypes that can cause latent or subclinical infections worldwide, suspicion, early diagnosis, and appropriate treatment are essential even in settings with limited resources.[@b01]--[@b03]

Multifocal myoclonic jerks are characterized by sudden, isolated, arrhythmic, asynchronous and asymmetric involuntary brief twitches, and jerks of muscles or muscle fibers involving various body areas, in particular the corners of the mouth, fingers, toes, limbs, several limbs, or a combination of limbs plus face, palate, head, jaw, neck, tongue, eyes, or trunk. Myoclonic jerks may have their origins at different levels of the nervous system and have many causes, and specialized tests such as video EEG, electromyography, and polysomnography are often necessary to ascertain its precise origin and accurate classification.[@b03]

Myoclonus may be cortical, subcortical, spinal, or peripheral in origin. Myoclonic jerking that is fleeting at the onset of sleep, or hypnic myoclonus, is considered physiological. It can be multifocal but seldom constant and lasting for minutes, when it may be pathological and indicative of an underlying neurological disorder as in our patient. Benign myoclonus can occur in healthy individuals and is most commonly caused by muscle contractions or during the induction of general anesthesia with intravenous etomidate and propofol or in benign fasciculation syndrome.[@b03]

Epilepsy syndromes and a variety of acquired factors, such as focal brain lesions, may cause cortical myoclonus. Subcortical myoclonus occurs mainly in toxic-metabolic encephalopathy, electrolyte disturbances, liver and respiratory failure, or as a reaction to several drugs. In cortical myoclonus, the electroencephalogram may be normal as seen in our patient, and this point was recently emphasized in a description of myoclonus in Wilson's disease.[@b02] Also, typical classification of physiological, hypnic, or hypnagogic jerks describes generalized jerks noted on falling asleep. The jerks observed in our patient presented within the first hour after sleep and they were multifocal.[@b03]

The differential diagnosis of myoclonus includes negative myoclonus, tremor, Parkinson's disease, CNS toxoplasmosis in HIV and acquired immune deficiency syndrome, and mitochondrial encephalopathy. Myoclonus may develop in response to neuroinfection, hyperosmolar hyperglycemic state, head or spinal cord injury, stroke, brain tumors or hypoxia, kidney or liver failure, lipid storage disease, chemical or drug poisoning, as a side effect of certain drugs such as tramadol, morphine, hydromorphine, pethidine, quinolones, benzodiazepine, gabapentin, sertraline, and lamotrigine. Myoclonus may also be present in multiple sclerosis, Parkinson's disease, Alzheimer's disease, opsoclonus myoclonus syndrome, Creutzfeldt--Jacob disease, Lyme disease, systemic lupus erythematosus, Tourette syndrome, and mitochondrial encephalomyopathy.[@b01]--[@b03] Clinical, video-imaging, laboratory and serological examination, radiological studies, and electrophysiological analysis should be performed to identify the underlying cause; however, electrophysiology was not performed in our patient. Analysis of the differential diagnoses showed no other disease that could explain our patient's reversible encephalopathy ([Table 3](#t03){ref-type="table"}).

Table 3Differential Diagnosis of the Causes of MyoclonusCausesDisease statesEndocrineHyperosmolar hyperglycemic stateIschemic statesBrain hypoxia, strokesVasculitisCNS vasculitisAutoimmuneSystemic lupus erythematosusDrugsTramadol, morphine, hydromorphine, pethidine, quinolones, benzodiazepine, gabapentin, sertraline, lamotrigine, and any drug or chemical poisoningInfection--sepsisNeurosyphilis, HIV encephalopathy, CNS toxoplasmosis in HIV-AIDS, Lyme diseaseNeurodegenerativeParkinson's disease, multiple sclerosis, Alzheimer's diseaseTraumaHead or spinal cord injuryNeoplasiaBrain tumors**Genetic**Mitochondrial encephalomyopathy, lipid storage diseaseOrgan failureKidney or liver failureOther causesNegative myoclonus, tremor, opsoclonus myoclonus syndrome, Creutzfeldt--Jacob disease, Tourette syndrome[^2]

We implemented Bayesian inference, response to treatment, and long-term follow-up for accuracy in diagnosis and here raise awareness of this rare movement disorder associated with serological evidence of a ubiquitous pathogen, whose role in epileptogenesis is being interrogated.

The treatment of myoclonus includes correction of the underlying cause such as electrolyte disturbances or, as in our case, specific antitoxoplasmosis therapy. However, if necessary, benzodiazepines such as clonazepam or antiepileptic drugs can be administered to suppress the symptoms in some patients.[@b03]

The hypothesized mechanism of the neurotoxicity in the pathogenesis of myoclonus is inhibition of gamma-aminobutyric acid receptors and activation of excitatory N-methyl-D-aspartate receptors, leading to a toxic encephalopathy.[@b01]--[@b03]

The authors thank the patient for allowing them to write this case report for teaching and medical education purposes. We also thank Dr. S. Karim for assisting with the preparation of the video.

**Funding:** None.

**Financial Disclosures:** None.

**Conflicts of Interest:** The authors report no conflict of interest.

**Ethics Statement:** The patient that appears on video has provided written informed consent; authorization for the videotaping and for publication of the videotape was provided.

[^1]: Abbreviations: BUN, Blood Urea Nitrogen; BsAG, B surface antigen; CMV, Cytomegalovirus; CRP, C-reactive Protein; CSF, Cerebrospinal Fluid; CT, Computed Tomography; DNA, Deoxyribonucleic Acid; EBV, Epstein--Barr Virus; EEG, Electroencephalogram; ELISA, Enzyme-linked Immunosorbent Assay; EMG, Electromyography; FTA-ABS, Fluorescent *Treponema Pallidum* Antibody Absorption; HIV, Human Immunodeficiency Virus; Ig, Immunoglobulin; MRI/MRA, Magnetic Resonance Imaging/Magnetic Resonance Angiography; PCR, Polymerase Chain Reaction; VDRL, Venereal Disease Research Laboratory; WBC, White Blood Cell.

[^2]: Abbreviations: AIDS, Acquired Immune Deficiency Syndrome; CNS, Central Nervous System; HIV, Human Immunodeficiency Virus.
