Pediatric Catatonia

Introduction

Catatonia is a syndrome with characteristic features, involving motor, speech, behavioral, and autonomic dysregulation. It is associated with neurodevelopmental, medical, neurologic, and neuropsychiatric disorders, as well as medication toxicity or withdrawal. Catatonia has similar characteristics and causes in children as in adults, but its recognition has lagged. It is frequently not recognized in the medical and psychiatric pediatric settings.

Background

In 1874, Karl Kahlbaum used the term “catatonia” to describe patients in a psychiatric ward with motor, speech, affective, and behavioral abnormalities. Subsequently, catatonia was used to define a subgroup of patients with schizophrenia. As catatonia was beginning to be recognized outside of the spectrum of psychiatric hospitals, Alan Gelenberg advised physicians, in a report in the Lancet in 1976, to consider catatonia in medical disorders. Further reports in the literature of catatonia in a variety of medical conditions, including infections, metabolic disorders, autoimmune disorders, and others, led to the revisions in the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition ( DSM-IV ), recognizing catatonia not only within the context of schizophrenia and mood disorders but also with general medical conditions. DSM-5 further differentiated catatonia from an independent condition to a specifier for neuropsychiatric and medical conditions.

Prevalence

In adults, catatonia has been reported in 7%–15% of patients in psychiatric hospitals and in approximately 35% of patients with schizophrenia. In an outpatient psychiatric population, 5.5% of adolescents were reported to have catatonia. In a group of youths receiving psychiatric treatment at a university hospital who were further selected for having a neuropsychiatric diagnosis known to increase risk for catatonia, 17.8% were identified to have catatonia. Catatonia has also been identified in 12%–17% of adolescents with autism. The prevalence rate of catatonia in an adult population attributed primarily to medical and not psychiatric disorders was reported at 21%. The prevalence rate of catatonia in pediatric medical conditions is not known because it is often unrecognized.

Screening

The most important screening tool for catatonia is awareness of the symptoms and maintaining a high index of suspicion. The symptoms, similar in adults and children, are detailed in Table 13.1 and include the 12 symptoms identified in DSM-5 , as well as other critical symptoms included in the Bush-Francis Catatonia Rating Scale (BFCRS). The threshold for considering the diagnoses of catatonia includes three or more symptoms from DSM-V criteria or two or more symptoms from the BFCRS, the preferred rating scale, given the high interrater reliability and validity. Relying only on DSM-5 criteria is inadequate given that the prevalence rates of symptoms not included in the DSM , such as staring and autonomic abnormalities, were found to be 74% and 32%, respectively.

Diagnosis

The diagnosis requires the following:

• 1.

  Comprehensive history (medical, neurologic, neuropsychiatric, pharmacotherapy)

• 2.

  Physical examination

• 3.

  Differentiation from other conditions such as delirium, neuroleptic malignant syndrome (NMS), serotonergic syndrome, and other conditions as listed in Table 13.2

  TABLE 13.2

  Differential Diagnoses

  Diagnosis	Definition	Differentiating Factors
  Delirium	An acute change from baseline with waxing and waning orientation	Motor dysregulation is not typical in delirium
  Neuroleptic malignant syndrome	Rigidity, hyperthermia, and autonomic dysfunction after exposure to neuroleptic medications	Caused by D2 antagonist History: medication administration with a temporal association to NMS onset Physical examination: fever, tremor, laboratory evidence of muscle injury (CK), leukocytosis Catatonia
  Toxic serotonin syndrome	Fever Twitching muscles Tremors Diarrhea Altered sensorium Hyperactive tendon reflexes Myoclonus Catatonia	Caused by excess serotonin Motor symptoms in serotonin syndrome classically do not include waxy flexibility or rigidity
  Complex partial seizures	Seizures characterized by change in awareness with a variety of motoric signs	EEG in catatonia should be normal. Both will respond to benzodiazepines, but catatonia should not respond to other antiepileptics
  Central nervous system (CNS) infection	Infections of different layers or components of the nervous system, which may affect behavior and consciousness	CNS infections often lack the motor findings classic of catatonia
  CNS neoplasm	Variety of pathologies, which may affect awareness and behavior by invasion or mass effect	Focal neurologic deficits should not be present with catatonia
  Inborn errors of metabolism	Variety of disorders, including urea cycle defects, MTHFR deficiency, porphyria, Wilson’s CTX, and Niemann-Pick
  Paranoia	Increased motor tone	No speech or behavioral symptoms
  Pharmacologic sedation	Decreased arousal due to medication administration	Motor features of catatonia are absent

  CK, creatine kinase; CTX, Cerebrotendinous xanthomatosis; EEG , electroencephalogram; MTHFR, methylene tetrahydrofolate reductase; NMS , neuroleptic malignant syndrome.

• 4.

  Investigation of underlying medical and neuropsychiatric disorders as listed in Table 13.3

  TABLE 13.3

  Catatonia—Underlying Medical and Neuropsychiatric Disorders

  Encephalitis	Infections	Herpes simplex
  		Malaria
  		Acquired immune deficiency syndrome
  		SLE
  	Autoimmune	NMDA-R-Ab
  		Hashimoto
  		Antiphospholipid syndrome
  		PANDAS/PANS
  		Epileptic encephalitis
  	Seizures	Epileptic encephalitis
  Genetic disorders		22q13.3 microdeletion
  Hypoventilation		Hypercapnia, hypoxemia
  Neurodevelopmental		Dandy-Walker
  Neuropsychiatric		Autism
  		Mood disorders
  		Schizoaffective disorders
  		OCD
  Metabolic		G6PD
  Thromboembolism		Pulmonary embolism, phlebitis
  Physical trauma		Burns
  		Head injury
  Psychologic trauma		Deprivation, abuse
  		Posttraumatic stress disorder
  Toxicity		Neuroleptics
  		Disulfiram
  		Steroids
  		Antibiotics
  		Wellbutrin
  		Baclofen
  		Recreational drugs
  		Venom
  Medication withdrawal		Benzodiazepines
  		Alcohol
  		Clozapine
  		Antidepressants
  		Gabapentin

  NMDA-R , N -methyl- d -aspartate receptor; OCD , obsessive-compulsive disorder; PANDAS/PANS , pediatric autoimmune neuropsychiatric disorders associated with streptococcus/pediatric acute-onset neuropsychiatric syndrome; SLE , systemic lupus erythematosus.

Laboratory Tests

Although there are no laboratory tests specific for catatonia, testing for underlying medical or neuropsychiatric disorders should be guided by the medical history and physical examination. These may include blood culture to check for infections or serum panels to test systemic lupus erythematosus (SLE) or D-dimer to check for a coagulopathy. A lumbar puncture may be necessary to obtain cerebral spinal fluid (CSF) if infections or autoimmune disorders such as N -methyl- d -aspartate receptor antibodies (NMDA-R) are suspected because serum may give false positives.

Electroencephalogram

There are no specific electroencephalogram (EEG) changes associated with catatonia. Low-amplitude background activity has been reported in some cases and high-amplitude slow activity in others. Catatonia has been reported in patients with seizure disorders and in patients where seizures are part of the underlying encephalopathy such as in NMDA-R Ab. Therefore obtaining an EEG may be helpful in the investigation of underlying conditions and in differentiating from delirium.

Brain Imaging

In a computerized tomography and functional magnetic resonance imaging (MRI) study of schizophrenic patients with catatonia, Northoff and colleagues reported enlargement of all inner and outer CSF spaces, mostly pronounced in the left frontal areas and alterations in laterality. Some studies report normal MRI findings. However, in a review of 95 adults with catatonia due to general medical or psychiatric conditions, 31 individuals (37.8%) had some abnormality on MRI and 16 individuals (19.5%) had a focal abnormality . This suggests that deciphering brain imaging findings that are related to catatonia or the underlying disorders is challenging.

Data from positron emission tomography (PET) using fluoro-deoxy-glucose (F-18-FDG-PET) indicate deficits in various brain regions. Schizophrenic patients with catatonia showed bilateral thalamic hypermetabolism and bilateral hypometabolism of frontal cortex. In a 19-year-old patient with a static encephalopathy and catatonia, bilateral occipitotemporal and thalamic hypometabolism were reported on FDG-PET. In a 20-year-old patient, where the catatonia and psychiatric symptoms were attributed to hypercapnia/hypoxemia, FDG-PET showed deficits in bilateral thalami, temporal cortices, and cerebellar while frontal and prefrontal cortices were less affected and there were no changes in striatum.

The brain metabolic changes seen with FDG-PET may be secondary to the catatonia or the underlying conditions. Flumazenil (FMZ)-PET changes may be more specific to catatonia, one study showing decreased benzodiazepine receptor binding in the right frontotemporal lobe area where FDG-PET showed glucose metabolism to be preserved. FMZ is a specific antagonist of γ-aminobutyric acid A (GABA _A ) receptors. Spectroscopy may also offer an even more specific tool because it can observe the combined glutamate and glutamine (glx) peak in vivo.