Frontal Lobe Syndrome in a Patient without Structural Brain Abnormalities

A 27-year-old man was admitted to our hospital because of depressed mood, severe insomnia, and suicidal ideations. Since early childhood the patient showed poor speech and language and symptoms of psychomotor and intellectual slowing. He finished secondary school at the age of 17 (usually 15–16 years) and was then employed in simple jobs. He suffered from auditory hallucinations, delusions, and illusionary misinterpretations for about 4 years. A first episode of catatonic stupor with waxy flexibility and catalepsy occurred 1 month prior to admission and further episodes were observed during his stay in our clinic, each of them associated with extreme anxiety and motor anosognosia. There was no indication of a head trauma, meningitis, or encephalitis in the patient’s medical history.

We observed a patient with impaired speech initiation, slowness and poverty of speech, verbal perseverations, and difficulties with the grammar but preserved language comprehension. Interestingly, the patient spoke only to very few individuals in the hospital who became familiar to him and trustworthy, which is consistent with a selective mutism, a behavioral trait reported to have existed since his first schooldays. However, his nonverbal social behavior was normal and there was no indication for symptoms of the autistic spectrum disorder. During his psychotic episode, our patient had even less drive than before, his motion was markedly slowed down and he was unable to recognize his personal situation; he was totally unconcerned in this respect. He was also indifferent to consequences of important decisions he made. Routine laboratory parameter testing, including drug screening, was normal, as were physical status and neurological examination. EEG, MRI, and [ ¹⁸ F]fluorodeoxyglucose positron emission tomography (FDG-PET) did not show any brain abnormalities. Cognitive functions were first assessed 10 weeks after admission when acute psychosis, catatonia, and depressive mood had remitted, and 19 weeks later with standardized neuropsychological testing procedures. 2 Medication consisted of risperidone (8 mg/day) and venlafaxine (300 mg/day). Cognitive performance was severely impaired in visual processing speed, alertness, selective and divided attention, verbal and visual working memory, verbal learning, and word fluency. In contrast, concept formation and reasoning were normal. The neuropsychological deficit pattern was similar 19 weeks later indicating that cognitive deficits were state- and not trait-dependent. Consistently, subscales (especially anergia) of the Brief Psychiatric Rating Scale (BPRS) 3 that cover motivation and initiation did not change over this period but were still the most affected items even 29 weeks after admission. In contrast, scores in the subscale for anxiety/depression of the BPRS (18 points) and in the Hamilton Depression Rating Scale (HAM-D) (30 points) 4 were clearly pathological at admission. These scores continuously dropped and remained stable ongoing from week 10 (BRPS=4–5; HAM-D=2–4 points).

This case demonstrates a complex neuropsychiatric pattern of cognitive deficits and psychopathological features that suggests a kind of frontal lobe symptom cluster which can be explained by regional prefrontal subsyndromes. The main cognitive and psychopathological symptoms can be explained by assuming supramodal executive dysfunction, which is characteristic for the “dysexecutive” (dorsal convexity system) and “apathetic” (mesial frontal system) types of regional prefrontal syndrome. 1 Positive symptoms such as delusions and hallucinations can be attributed to prefrontal and medial temporal dysfunction. 5, 6 Following Northoff, 7 catatonic symptoms as shown by the patient may be due to impaired connectivity from orbitofrontal to premotor/motor cortex resulting in dysregulation of the motor loop during emotional stimulation, visible as akinesia. In addition, the difficulty in initiating actions may be attributed to a disorder of the so-called “willed action system” that includes the dorsolateral prefrontal cortex, the anterior cingulated cortex, the anterior supplementary motor area and fronto-striatal circuits. Alterations of the orbitofrontal cortex may result in D ₂ -receptor down-regulation of the caudate nucleus and may thus cause waxy flexibility. Motor anosognosia is thought to be a result of the dysfunction of ventrolateral prefrontal cortex and subsequent network disturbances between the right ventrolateral prefrontal cortex, right dorsolateral prefrontal cortex, and right posterior parietal cortex. Orbitofrontal cortex dysfunction during negative emotional processing with subsequent hyperactivity of the anterior cingulated cortex and medial prefrontal cortex may mediate catatonic stupor and akinetic mutism. Similarly, selective mutism, a form of social phobia/social anxiety disorder, can be regarded as a “motivational disorder” suggesting an involvement of the dorsolateral prefrontal cortex as an essential part of the “willed action system.” Indeed, Tillfors et al. 8 found an activation of the amygdala, dorsolateral prefrontal cortex and inferior temporal cortex when subjects with social anxiety disorder were exposed to a public speaking task to provoke anxiety-related symptoms.

Although the etiology remains unclear, patient’s speech and language disturbance fits in a “congenital” form of Broca’s type or nonfluent aphasia (left inferior frontal cortex). Cognitive deficits occurred mainly in the executive domain (sustaining and dividing attention, verbal learning strategy, working memory, and cognitive flexibility), while verbal memory, concept formation, and reasoning were spared. According to Stuss et al., 9 these executive deficits can be attributed to dorsolateral and medial prefrontal dysfunction.

In conclusion, anatomic regions suggested to be affected in our patient include prefrontal association cortex regions that have often been associated with neuropsychiatric disorders (dorsolateral, ventrolateral and medial prefrontal cortex, orbitofrontal cortex, and anterior cingulated cortex), but also parts of the motor cortex including the left inferior frontal lobe and the supplementary motor area. Because cortical/subcortical structural damage in the MRI scan as well as signs of “hypofrontality” in the PET study were absent in our patient, it remains open whether impaired connectivity between different brain regions might have caused both functional hyperactivity of some regions (e.g., dorsolateral prefrontal cortex in selective mutism) and hypoactivity of others (e.g., orbitofrontal cortex and supplementary motor area in executive dysfunction), respectively. Thus, regional frontal lobe syndromes, including neuropsychiatric symptoms, may be present without any signs of structural abnormalities. In contrast to the case reported by Ferrara et al., 10 structural and functional neuroimaging was not a helpful tool for diagnosis in our patient, but detailed neuropsychological and psychopathological examinations were.

We thank Anna Wendl for her professional assistance in neuropsychological testing.