244 http://neuro.psychiatryonline.org J Neuropsychiatry Clin Neurosci 20:2, Spring 2008

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Frontal Lobe Syndrome in aPatient without StructuralBrain Abnormalities

To the Editor: The frontal lobe playsan important role in guiding andsupervising complex behavior. De-pending on the location of the in-jury, manifestations of frontal lobedysfunction range from cognitive(executive) decits to akinesia andmutism to changes in personality.1

Here we present a case with neuro-psychiatric symptoms mimicking afrontal lobe syndrome in the ab-sence of structural brain abnormali-ties.

Case ReportA 27-year-old man was admitted toour hospital because of depressedmood, severe insomnia, and sui-cidal ideations. Since early child-hood the patient showed poorspeech and language and symp-toms of psychomotor and intellec-tual slowing. He nished secondaryschool at the age of 17 (usually 1516 years) and was then employed insimple jobs. He suffered from audi-tory hallucinations, delusions, andillusionary misinterpretations forabout 4 years. A rst episode of cat-atonic stupor with waxy exibilityand catalepsy occurred 1 monthprior to admission and further epi-sodes were observed during hisstay in our clinic, each of them as-sociated with extreme anxiety andmotor anosognosia. There was noindication of a head trauma, menin-gitis, or encephalitis in the patientsmedical history.

We observed a patient with im-paired speech initiation, slownessand poverty of speech, verbal per-severations, and difculties withthe grammar but preserved lan-guage comprehension. Interestingly,the patient spoke only to very fewindividuals in the hospital who be-

came familiar to him and trustwor-thy, which is consistent with a se-lective mutism, a behavioral traitreported to have existed since hisrst schooldays. However, his non-verbal social behavior was normaland there was no indication forsymptoms of the autistic spectrumdisorder. During his psychotic epi-sode, our patient had even lessdrive than before, his motion wasmarkedly slowed down and he wasunable to recognize his personal sit-uation; he was totally unconcernedin this respect. He was also indiffer-ent to consequences of importantdecisions he made. Routine labora-tory parameter testing, includingdrug screening, was normal, aswere physical status and neurologi-cal examination. EEG, MRI, and[18F]uorodeoxyglucose positronemission tomography (FDG-PET)did not show any brain abnormali-ties. Cognitive functions were rstassessed 10 weeks after admissionwhen acute psychosis, catatonia,and depressive mood had remitted,and 19 weeks later with standard-ized neuropsychological testingprocedures.2 Medication consistedof risperidone (8 mg/day) and ven-lafaxine (300 mg/day). Cognitiveperformance was severely impairedin visual processing speed, alert-ness, selective and divided atten-tion, verbal and visual workingmemory, verbal learning, and worduency. In contrast, concept forma-tion and reasoning were normal.The neuropsychological decit pat-tern was similar 19 weeks later in-dicating that cognitive decits werestate- and not trait-dependent. Con-sistently, subscales (especially aner-gia) of the Brief Psychiatric RatingScale (BPRS)3 that cover motivationand initiation did not change overthis period but were still the mostaffected items even 29 weeks afteradmission. In contrast, scores in thesubscale for anxiety/depression ofthe BPRS (18 points) and in the

Hamilton Depression Rating Scale(HAM-D) (30 points)4 were clearlypathological at admission. Thesescores continuously dropped andremained stable ongoing from week10 (BRPS45; HAM-D24points).

CommentThis case demonstrates a complexneuropsychiatric pattern of cogni-tive decits and psychopathologicalfeatures that suggests a kind offrontal lobe symptom cluster whichcan be explained by regional pre-frontal subsyndromes. The maincognitive and psychopathologicalsymptoms can be explained by as-suming supramodal executive dys-function, which is characteristic forthe dysexecutive (dorsal convex-ity system) and apathetic (mesialfrontal system) types of regionalprefrontal syndrome.1 Positivesymptoms such as delusions andhallucinations can be attributed toprefrontal and medial temporaldysfunction.5,6 Following Northoff,7

catatonic symptoms as shown bythe patient may be due to impairedconnectivity from orbitofrontal topremotor/motor cortex resulting indysregulation of the motor loopduring emotional stimulation, visi-ble as akinesia. In addition, the dif-culty in initiating actions may beattributed to a disorder of the so-called willed action system thatincludes the dorsolateral prefrontalcortex, the anterior cingulated cor-tex, the anterior supplementary mo-tor area and fronto-striatal circuits.Alterations of the orbitofrontal cor-tex may result in D2-receptor down-regulation of the caudate nucleusand may thus cause waxy exibil-ity. Motor anosognosia is thoughtto be a result of the dysfunction ofventrolateral prefrontal cortex andsubsequent network disturbancesbetween the right ventrolateral pre-frontal cortex, right dorsolateralprefrontal cortex, and right poste-

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rior parietal cortex. Orbitofrontalcortex dysfunction during negativeemotional processing with subse-quent hyperactivity of the anteriorcingulated cortex and medial pre-frontal cortex may mediate cata-tonic stupor and akinetic mutism.Similarly, selective mutism, a formof social phobia/social anxiety dis-order, can be regarded as a moti-vational disorder suggesting aninvolvement of the dorsolateral pre-frontal cortex as an essential part ofthe willed action system. Indeed,Tillfors et al.8 found an activation ofthe amygdala, dorsolateral prefron-tal cortex and inferior temporal cor-tex when subjects with social anxi-ety disorder were exposed to apublic speaking task to provokeanxiety-related symptoms.

Although the etiology remainsunclear, patients speech and lan-guage disturbance ts in a congen-ital form of Brocas type or non-uent aphasia (left inferior frontalcortex). Cognitive decits occurredmainly in the executive domain(sustaining and dividing attention,verbal learning strategy, workingmemory, and cognitive exibility),while verbal memory, concept for-mation, and reasoning were spared.According to Stuss et al.,9 these ex-ecutive decits can be attributed todorsolateral and medial prefrontaldysfunction.

In conclusion, anatomic regionssuggested to be affected in our pa-tient include prefrontal associationcortex regions that have often beenassociated with neuropsychiatricdisorders (dorsolateral, ventrola-teral and medial prefrontal cortex,orbitofrontal cortex, and anteriorcingulated cortex), but also parts ofthe motor cortex including the leftinferior frontal lobe and the supple-mentary motor area. Because corti-cal/subcortical structural damage inthe MRI scan as well as signs ofhypofrontality in the PET studywere absent in our patient, it re-

mains open whether impaired con-nectivity between different brain re-gions might have caused bothfunctional hyperactivity of some re-gions (e.g., dorsolateral prefrontalcortex in selective mutism) and hy-poactivity of others (e.g., orbitofron-tal cortex and supplementary motorarea in executive dysfunction), re-spectively. Thus, regional frontallobe syndromes, including neuro-psychiatric symptoms, may be pres-ent without any signs of structuralabnormalities. In contrast to thecase reported by Ferrara et al.,10

structural and functional neuroim-aging was not a helpful tool for di-agnosis in our patient, but detailedneuropsychological and psycho-pathological examinations were.

We thank Anna Wendl for her pro-fessional assistance in neuropsychologi-cal testing.

Johannes M.H. Hennings, M.D.Thomas C. Wetter, M.D.

Max Planck Institute of Psychi-atry, Munich, Germany

Josef Zihl, Ph.D.Max Planck Institute of Psychi-atry, Munich, GermanyDepartment of Psychology,University of Munich,Germany

References

1. Duffy JD, Campbell JJ: Regional pre-frontal syndromes: a theoretical andclinical overview, in Principles of Fron-tal Lobe Function. Edited by Stuss DT,Knight RT. Oxford, England, OxfordUniversity Press, 2002, pp 113123

2. Lezak MD, Howieson DB, Loring DW:Neuropsychological Assessment, 4thed. Oxford, England, Oxford Univer-sity Press, 2004

3. Overall JE, Gorham DR: The brief psy-chiatric rating scale, in ECDEU Assess-ment Manual for Psychopharmacology,Revised. Edited by Guy W. NationalInstitutes of Mental Health, Rockville,Md., 1976, pp 157169

4. Hamilton M: A rating scale for depres-sion. J Neurol Neurosurg Psychiatry1960; 23:5662

5. Liddle PF: Schizophrenic syndromes,cognitive performance and neurologi-cal dysfunction. Psychol Med 1987;17:4957

6. Weinberger DR: Implications of normalbrain-development for the pathogene-sis of schizophrenia. Arch Gen Psychia-try 1987; 44:660669

7. Northoff G: What catatonia can tell usabout top-down modulation: a neu-ropsychiatric hypothesis. Behav BrainSci 2002; 25:555577

8. Tillfors M, Furmark T, Marteinsdottir I,et al: Cerebral blood ow during antic-ipation of public speaking in socialphobia: a PET study. Biol Psychiatry2002; 52:11131119

9. Stuss DT, Alexander MP, Floden D, etal: Fractionation and localization ofdistinct frontal lobe processes: evidencefrom focal lesions in humans, in Princi-ples of Frontal Lobe Function. Editedby Stuss DT, Knight RT. Oxford, En-gland, Oxford University Press, 2002,pp 392407

10. Ferrara M, Freda F, Massa R, et al:Frontal lobe syndrome or adolescent-onset schizophrenia? A case report.Acta Psychiatr Scand 2006; 114:375377

Neuroimaging Correlates ofChronic Delusional Jealousyafter Right CerebralInfarction

To the Editor: Although there havebeen accounts of delusional jeal-ousy occurring in patients withstructural brain damage, the phe-nomenon has rarely been reportedfollowing right cerebrovascular in-farction. In this new case we willendeavor to describe the possiblepathogenic role of right hemispherelocalization.

During hospitalization for a tran-sient left-sided hemiplegia after aright middle cerebral artery infarct,a 77-year-old man became con-vinced that members of the medicalstaff wanted to steal his house. Al-though he was rapidly discharged(5 days later), he subsequently de-clared that his wife had had a loveaffair with a school master many