Tourette syndrome (TS) is a condition wherein motor and vocal tics occur, provoked by an urge, but often not able to be completely voluntarily controlled. Tics are known to cause physical and emotional risks to quality of life, and in rare extreme cases, may have permanent consequences. We report the first cases, to our knowledge, of rhabdomyolysis due to extreme tic fits in two distinct patients with TS. Both patients presented with severe tics, leading to elevated creatine kinase and a diagnosis of rhabdomyolysis requiring hospitalisation and intravenous fluids. Neither had neuroleptic malignant syndrome. One patient was on concurrent neuroleptic therapy, but his laboratory parameters improved when tics subsided despite continued neuroleptic use. Our cases highlight the potential complication of rhabdomyolysis secondary to severe tic fits independent of neuroleptic use.
- movement disorders (other than parkinsons)
- medical management
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Tourette syndrome (TS) is a condition wherein motor and vocal tics occur, often provoked by an urge, but not able to be completely voluntarily controlled. Many patients respond, at least partially, to behavioural and pharmacologic interventions, but some cases remain treatment-refractory and severely disabled. ‘Malignant’ TS has been reported to cause self-injury, hospitalisations, and in extreme cases, permanent complications, such as cervical myelopathy and eye enucleation.1 2 Rhabdomyolysis is a syndrome characterised by muscle necrosis and elevated creatine kinase (CK) with or without myoglobinuria.3 4 We present the first cases, to our knowledge, of rhabdomyolysis due to extreme tic fits in two distinct patients with severe TS.
Case presentation—case 1
A 12-year-old boy with a history of attention deficit hyperactivity disorder (ADHD), social anxiety and post-traumatic stress disorder, presented with severe TS. Apart from this, the developmental history and cognition were normal. Tic onset was at age 8, with eye blinking, shoulder/neck jerking and snorting. Family history included ADHD and depression in his siblings, tics in his father and substance abuse in both parents. Tics became more complex over time, including coprolalia and echolalia. At age 11, he had dramatic escalation in tic frequency and severity, with constant thrusting of trunk and limbs, screaming and coprolalia, requiring three hospitalisations for management of tic exacerbation and associated rhabdomyolysis. On presentation, his regimen included aripiprazole 2 mg and clonidine 0.1 mg every night, guanfacine 4 mg daily and methylphenidate 54 mg daily.
During his first hospitalisation, (figure 1A), his total CK increased to 6953 U/L (normal <200 U/L). He was afebrile; labs showed mildly elevated creatinine 65 µmol/L (blood urea nitrogen (BUN)/creatinine 23). A urine drug screen, C reactive protein, liver and thyroid function were normal. Aripiprazole was discontinued, given the potential to be a confounding cause of elevated CK.
Outcome and follow-up—case 1
His CK improved with intravenous fluids, but unfortunately, he was re-hospitalised within 10 days of discharge for recurrent tic exacerbation, including repeated episodes of forceful muscle stiffening tics of both arms and legs unresponsive to oral lorazepam with mildly elevated CK (up to 631 U/L; figure 1A). Metabolic workup was otherwise unremarkable. He was discharged after a dose of intramuscular haloperidol; his clonidine was increased and low-dose clonazepam given for prolonged tics. When evaluated in clinic (total Yale Global Tic Severity Score (YGTSS) of 92), low-dose risperidone was initiated for ongoing management of severe tics. Notably, his CK normalised as tics began to decrease, while remaining on low-dose risperidone (figure 1A). However, he was re-hospitalised 7 months afterwards for recurrent rhabdomyolysis in the setting of severe tic exacerbation (total CK up to 1054 U/L; figure 1A). His tics included yelling and prolonged episodes of muscle tensing of his neck, trunk and extremities. One dose of ziprasidone together with intravenous fluids improved his CK at time of discharge, again in the context of continued neuroleptic use (risperidone total 2 mg/day).
Case presentation—case 2
A 16-year-old boy with a history of TS, ADHD, depression and anxiety presented with an acute tic exacerbation. Developmental history and cognition were normal. Tic onset was at age 3, including motor tics of eye blinking and rolling, lip pouting, head and shoulder jerking, truncal tensing and limb extension, along with vocal tics, including sniffing, barking or screaming. He had a family history of anxiety and obsessive compulsive disorder (OCD). He failed numerous medications due to inefficacy or adverse effects, including clonidine, guanfacine, clonazepam, lorazepam, topiramate, fluphenazine, haloperidol, risperidone, aripiprazole and pimozide. He was not on neuroleptics for 6 months prior to and including the presenting issue.
He presented to the emergency department after developing worsened tics, including large amplitude head and body jerks, violent thrashing movements, self-injurious behaviour (punching himself), screaming and grunting nearly continuously. His YGTSS was 95.
He was afebrile and euvolemic. He had an initial CK elevation of 2682 U/L (figure 1B). His liver enzymes were mildly elevated at aspartate transaminase 87 IU/L and alanine aminotransferase 68 IU/L, with a normal alkaline phosphatase at 80 IU/L. His creatinine was within normal limits (86 µmol/L) and BUN was at the upper limit of normal at 7.5 mmol/L. Thyroid function was not performed. Although a drug screen was not ordered, the patient denied any illicit drug use.
Outcome and follow-up—case 2
A total of 4 mg of intravenous lorazepam did not significantly improve his tic fits. Because of concern for worsening rhabdomyolysis, he was admitted to the paediatric intensive care unit and placed on intravenous fluids and a dexmedetomidine infusion in an attempt to cease ongoing severe tics, muscle activity and self-injurious behaviour by sedating and placing under close observation. He was unable to tolerate the dexmedetomidine due to symptomatic bradycardia. He subsequently received 1 g of intravenous valproate load, with maintenance oral dose of 500 mg two times per day due to previous reports of valproic acid showing possible benefit in refractory TS in addition to a potential mood stabilisation effect. His tics decreased and his CK trended down, with the last value being 1033 U/L before discharge (figure 1B). He was placed on deutetrabenazine at discharge, titrating up to 6 mg two times per day.
TS may cause disability due to tics, comorbid conditions, such as anxiety, OCD and ADHD, and due to secondary complications of living with tics. Social embarrassment, exacerbating concomitant mood disorders, can contribute to disability in patients with TS.5 Rare but severe complications of TS include cervical myelopathy, cervical disc herniation with spinal cord compression, vertebral artery dissection with stroke and bilateral self-induced retinal detachment.2 6 There may also be a risk of secondary systemic insult. As demonstrated in our two cases, rhabdomyolysis due to extreme, continuous and intense tics is an important rare complication to be aware of.
TS patients often have psychiatric or behavioural comorbidities, which further exacerbate the tic fits that can lead to rhabdomyolysis. The contribution of mood dysregulation can be difficult to disentangle, but the frequency and intensity of tic movements can create the risk of secondary complications. Rhabdomyolysis is a pathological condition of skeletal muscle damage that leads to toxic intracellular material being released into blood circulation, including myoglobin, CK and electrolytes.3 Serum CK is the most sensitive enzyme indicator of muscle injury, with an elevation of five times the upper limit of normal in the absence of cardiac or brain infarction already indicating significant muscle damage.4 Other hyperkinetic movement disorders have been shown to be associated with rhabdomyolysis, including dystonic storm, generalised chorea and severe levodopa-induced dyskinesias in Parkinson’s disease.7 8 Tics are also hyperkinetic movements that can lead to secondary rhabdomyolysis, and those with more severe, continuous tics involving the trunk and large muscle groups for prolonged periods of time are likely at a higher risk. Potential complications of rhabdomyolysis should be monitored for, including myoglobinuria, acute renal failure, fluid and electrolyte abnormalities, and disseminated intravascular coagulation.4
In patients with TS presenting with rhabdomyolysis, other important and common differential diagnoses to consider include neuroleptic malignant syndrome (NMS), serotonin syndrome and hypothyroidism. Concomitant use(s) of neuroleptics in this population (even at low doses, such as risperidone 0.25 mg once daily9), as well as selective serotonin reuptake inhibitors (SSRIs) for comorbid depression, anxiety and OCD, may be important risk factors for NMS and serotonin syndrome, respectively. In our patients, neither met criteria for NMS,10 lacking rigidity, hyperthermia and autonomic dysfunction, and neither was taking SSRI medication. Case 2 was not on neuroleptic therapy and case 1 was on stable low dose (risperidone 2 mg/day), which he tolerated before and after the periods of extreme tics, with improvement in CK despite continued therapy. Psychostimulant use has not clearly been associated with worsening tics,11 12 but in some individuals may influence tic severity. In case 1, the stimulant dosage remained stable throughout the tic fits and during subsequent improvement and case 2 was not on a psychostimulant during time of his severe tic fits. For complete workup of elevated CK in children with TS, one should also consider initial presentation of systemic lupus erythematous. Other causes of increased agitation leading to worsened tics should be considered, including behavioural dyscontrol, illicit drug intoxication or withdrawal, central nervous system or systemic infections, trauma, pheochromocytoma or porphyria.13
The motor and vocal tics seen in our patients were extremely severe and included high amplitude movements and self-injurious behaviour. The exceptional choice of a dexmedetomidine infusion in case 2 was for use as a sedating agent to control the tics in an attempt to prevent further muscle breakdown and self-injury. To our knowledge, there are no prior reports of usage of dexmedetomidine for treatment of severe tics and we would presently not recommend its routine use. Also, the use of valproate for severe tics showed promise in several reported case series, but this benefit did not carry through when a systematic review and meta-analysis was conducted, and thus, it is not recommended for routine use in TS.14 Management in these situations is complex and involves simultaneously managing the rhabdomyolysis as well as reducing tics, agitation and anxiety. Comorbid mood and behavioural issues need to be identified and addressed, commonly requiring stabilisation in the hospital, but continued management after discharge.
We report two unique cases of rhabdomyolysis secondary to severe tic fits in TS. We add to growing amount of severe complications seen in severe TS. NMS is an important diagnostic consideration in TS patients with severe tics and elevated CK with concurrent neuroleptic use. However, rhabdomyolysis, independent of NMS or neuroleptic use, can occur secondary to severe TS and is an important complication that clinicians should be aware of.
We report two unique cases of rhabdomyolysis secondary to severe tic fits in patients with Tourette syndrome.
Rhabdomyolysis, independent of neuroleptic malignant syndrome or neuroleptic use, should be considered as a potential complication caused by severe tics.
In addition to recognising presenting signs early, aggressive management of rhabdomyolysis and violent tics is critical in preventing further systemic and neurological complications.
Contributors All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by KLKA, SYC and IAM. The first draft of the manuscript was written by KLKA and all authors reviewed, commented on and edited previous versions of the manuscript. All authors read and approved the final manuscript.
Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.
Competing interests None declared.
Patient consent for publication Parental/guardian consent obtained.
Provenance and peer review Not commissioned; externally peer-reviewed.
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