Beware ictal activity that mimics psychiatric illness

Table 2

Differential diagnosis of NCSE

Metabolic disorders	Hypo/hyperglycemia, hypercalcemia, Addison’s disease, Cushing’s disease, uremia
Neurologic disorders	Stroke, CNS tumors, closed head trauma, transient global amnesia, seizures, inflammatory and infectious encephalopathies
Psychiatric disorders	Schizophrenia, mood disorders, catatonia, malignant catatonia, somatoform disorders, conversion disorder, Asperger’s syndrome, malingering
Toxic disorders	Toxic encephalopathy, neuroleptic malignant syndrome, serotonin syndrome, alcohol and sedative-hypnotic withdrawal, drugs (lithium toxicity, tricyclics, baclofen, tiagabine, overdose)
Source: Reference 17,18

NCSE in the elderly can be difficult to diagnose, especially in patients with comorbid severe medical illnesses and other confusional states.⁴CPSE with possible generalization is more common than ASE in the elderly. Hyperreligiosity, intermittent agitation, motor perseveration, ictal fear, catatonic signs, delusional preoccupation, and auditory and visual hallucinations have been observed during NCSE in the elderly and misdiagnosed as primary psychiatric conditions.

Cerebrovascular disease, tumors, and trauma are the most common causes of late-life NCSE.^4,19 De novo NCSE occasionally presents:

• after benzodiazepine withdrawal
  
• with neuroleptic, tricyclic antidepressant, or lithium treatment^10,16
  
• with metabolic abnormalities and nonpsychotropic medications.¹⁰
  

Clinical symptoms

Clinical features of NCSE include cognitive changes, speech abnormalities, affective disturbances, psychosis, poor impulse control, and bizarre behaviors (Table 3). Some patients develop ictal phenomena resembling catatonia or clinical and EEG changes that mimic neuroleptic malignant syndrome (NMS).^20-23

Table 3

Clinical features that raise suspicion of NCSE

Domain	Features
Cognitive changes	Prolonged confusion, executive dysfunction, obtundation, attention/memory difficulties, lack of initiative, perseveration, stupor
Speech	Poverty of speech with monosyllabic answers, verbal perseveration, echolalia, palilalia, aphasia, paraphasic errors, confabulation, mutism
Affective	Prolonged fear, affective indifferent state with blank facial expression, hypomania, psychotic depression, inappropriate laughing and crying, anxiety states
Psychosis	Visual, auditory and cenesthetic hallucinations, delusions
Impulse control	Hostility, agitation, violence, groping, genital manipulation, picking, posturing
Others	Catatonic signs, autonomic disturbances
Source: References 5,7-9,12,15-17,20-23

Catatonia. Lim et al²⁴ described three patients with EEG-confirmed NCSE that manifested as ictal catatonia. A prolonged, trance-like, stuporous state during epilepsy has been reported, as has CPSE presenting with psychogenic unresponsiveness. Drury et al²⁵ described a patient who presented with catatonia and increased muscle tone but had prominent EEG abnormalities implicating an organic cause.

Among 29 patients with acute catatonic syndromes, epileptic activity was identified in 4. One patient with absence status was diagnosed with NMS during the catatonic period.²⁶ Conversely, the commonality of clinical features has led to misdiagnosis of psychogenic catatonia as NCSE. EEG is necessary to exclude NCSE in these cases.

NMS. Yoshino et al²⁷ described two patients taking neuroleptics who met criteria for NMS and had EEG changes consistent with NCSE. They later reported another patient with NCSE complicating NMS; the point at which NCSE developed was unknown, however, because EEG activity was not recorded at NMS onset.²⁸ Based on NMS diagnostic criteria proposed by Caroff et al,²⁹ these patients could have developed NCSE mimicking NMS.

EEG for diagnosis

Candidates. Because differentiating NCSE from similar conditions can be difficult, use EEG to confirm your clinical observations. No guidelines exist, but consider EEG when the patient’s history suggests NCSE. Ask the patient or family about:

• changes in mental status from baseline, especially new-onset catatonia or unexplained altered consciousness
  
• duration of events
  
• presence or absence of motor activity
  
• behavioral fluctuations
  
• presence or absence of automatisms or blinking.
  

List the patient’s medications, ask about illicit substance or alcohol use, and gather a comprehensive history of medical, neurologic, and psychiatric illnesses. Include NCSE in the differential diagnosis of elderly patients with acute prolonged confusion. Try to obtain EEG early to differentiate focal from secondary generalized seizures.

EEG patterns. Table 4 summarized NCSE diagnostic criteria. NCSE shows characteristic patterns in ASE and CPSE,^9,10,16,23 and EEG changes can be continuous or nearly continuous in both.

Table 4

EEG findings that support a clinical diagnosis of NCSE

Clear-cut criteria
Frequent or continuous focal seizures, with ictal patterns that wax and wane with change in amplitude, frequency, and/or spatial distribution
Frequent or continuous generalized spike wave discharges:
in patients without history of epilepsy in patients with epilepsy, when discharges show significant changes in intensity or frequency compared with baseline EEG
Periodic lateralized epileptiform discharges (“PLEDs”) or bilateral periodic epileptiform discharges (“biPEDs") occurring in patients with coma from generalized tonic-clonic status epilepticus (subtle SE)
Probable (equivocal) criteria
Patients with acute cerebral damage who also show frequent or continuous EEG abnormalities without previous similar findings
Patients with epilepsy who show frequent or continuous generalized EEG abnormalities and similar interictal EEG patterns but whose clinical symptoms suggest NCSE
Source: References 4,12-14,17

In ASE, a generalized, bilaterally synchronous, rhythmic, 3- to 3.5-second spike with a bifrontal maximum is seen in 40% of cases.³⁰ Also described in ASE are fragmented spike waves, multiple spikes and waves, and generalized bilateral discharges with focal predominance. This last pattern might suggest an underlying focal origin of the epileptic discharge with secondary generalization.