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Clinical and Research Reports   |    
Schizophrenia-Like Presentation of Neuroacanthocytosis
Marie-Andrée Bruneau, M.D., M.Sc., FRCPC; Paul Lespérance, M.D., M.Sc., FRCPC; Sylvain Chouinard, M.D.
The Journal of Neuropsychiatry and Clinical Neurosciences 2003;15:378-380. doi:10.1176/appi.neuropsych.15.3.378
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NeuroacanthocytosisSchizophreniaPsychosisChorea

Received October 2, 2001; revised January 8, 2002; accepted March 19, 2002. From the Departments of Neurology and Psychiatry, Movement Disorder Clinic, CHUM-Notre-Dame Hospital, University of Montreal, Montreal, Quebec, Canada; Neurogenetic Clinic, Montreal General Hospital, Montreal, Quebec, Canada; McGill University, Montreal, Quebec, Canada. Address correspondence to Dr. Marie-Andrée Bruneau, CHUM, Hôpital Notre-Dame Département de psychiatrie Service de Consultation-Liaison 1560 Sherbrooke Est Montréal, Québec, Canada H2L 4M1 (514) 890-8000-2 # 5661; ma.bruneau@sympatico.ca (E-mail).

A rare disorder, neuroacanthocytosis is characterized by chorea, tics, subcortical cognitive impairments, and acanthocytosis. This study presents two men with neuroacanthocytosis who were initially diagnosed with schizophrenia. Findings revealed the intricate relationships between movement disorders and psychosis and the importance of accurate diagnoses.

Abstract Teaser
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Arare, putative autosomal recessive disorder, neuroacanthocytosis was first identified in 1968. Major symptoms, which include chorea, motor and vocal tics, and axonal neuropathy with amyotrophy, are often unexpressed until the third decade. Acanthocytes are found in the blood smear. Generalized seizures are present in one-half of all reported cases, and features of parkinsonism, supranuclear palsy, or dystonia may also be present.1,2,3,4 A number of patients show cardiac abnormalities when screened, and self-mutilation of the lips and tongue has been described. Neuroacanthocytosis shares common features with Huntington's disease (e.g., neuropathological changes, chorea).5

Characterized by a subcortical type of dementia,6,7 cognitive impairment causes deficiencies in executive functions, working memory, and visuopraxic abilities. Less commonly reported are behavioral and psychiatric manifestations. Patients may experience personality alterations of a frontal type (e.g., impulsiveness, irritability, lack of concentration, or apathy).4,6 Reports of psychosis, obsessive-compulsive disorder, anxiety, and depression are less common.4,6,8,9

In diagnosing neuroacanthocytosis, a blood smear must be performed, and an acanthocyte count of more than 3% must be verified. A lipoprotein profile is usually normal, but an increase in serum creatine kinase (CK) should be observed. To eliminate other conditions, such as Huntington's disease or McLeod syndrome, genetic testing should be done; and a blood type must be determined. Electro/echocardiography, muscle biopsy, neuroimagery, and neuropsychology tests ususally complete the investigation.

Here, we examine case reports for two patients, Mr. B and Mr. S. Both men were initially diagnosed with schizophrenia, and later investigations revealed that they suffered from neuroacanthocytosis.

Mr. B, a 40 year-old man currently living in a supervised home, was first hospitalized in 1977 at age 18 for an acute psychotic reaction. While drug abuse was ruled out, Mr. B was described as withdrawn, depressed, paranoid, and suicidal, and he stopped going to school. He was treated with various antipsychotic drugs, such as thioridazine, chlorpromazine, and loxapine. A blood smear revealed that he had neutrophilic leucocytosis and acanthocytosis, and a neurological exam showed that he had difficulties with rapid alternating movements and an absence of deep tendon reflexes. From 1978 to 1983, Mr. B was hospitalized four times and diagnosed with paranoid schizophrenia or schizophreniform disorder. He demonstrated paranoid and religious ideas, loose association of thought, and visual hallucinations. He appeared aggressive, disoriented, and, occasionally, lost in time. He also complained of headaches and dizziness. Every time a blood test was performed, the complete blood count showed the same abnormalities. Treatment for Mr. B included haloperidol, mesoridazine, fluphenazine with lithium, and anticholinergics.

In 1983, Mr. B began to show signs of movement disorder. A neurological consultation concluded that he was suffering from essential tremor, tics, and tardive dyskinesia. Subsequently, he received more anticholinergics. From 1983 to 1998, Mr. B was hospitalized six times, and his diagnosis changed to undifferentiated schizophrenia. He became more agitated and aggressive, and he was incoherent, with complete loss of insight. The choreiform movement disorder worsened, with abnormal balance problems and parkinsonian features. An electromyography (EMG) performed in 1989 showed an axonal polyneuropathy. Lab tests always revealed hematological abnormalities and an increased level of hepatic enzymes. Mr. B was further treated with loxapine, chlorpromazine, haloperidol, flupenthixol, and fluphenazine with lithium. His treatment was changed to pimozide after a neurologist suspected that symptoms were indicative of spinocerebellar degeneration.

In 1998, Mr. B was hospitalized for agitation, sleep problems, and urinary incontinence. Due to elevated levels of CK, neuroleptic malignant syndrome was suspected. Subsequently, all neuroleptic medication was withdrawn, and he was treated with dantrolene and diazepam. After resolution, a treatment with clozapine and valproic acid was introduced. In February 1999, a new consulting neurologist suspected neuroacanthocytosis and referred the patient to our clinic for diagnosis confirmation. In retrospect, we wondered if Mr. B's psychiatric illness was the first presentation of his neuroacanthocytosis or if the two illnesses (schizophrenia and neuroacanthocytosis) were coincidental in the same patient.

In the second case, Mr. S, a 39-year-old man, had a family history that was positive for undetermined psychiatric illnesses. He had two paternal uncles, three paternal aunts, and a paternal grandmother who all suffered from some form of psychiatric illness. Additionally, his father was diagnosed with schizophrenia and suffered from movement disorders. Mr. S, who never worked or married, was described as having a schizoid personality type since youth. When he was 17 years old, a psychiatrist suspected that he was schizophrenic. He wasn't hospitalized for psychiatric problems until he was 35 years old, in 1995. Reasons for hospital admittance included paranoid ideas, agitation, visual and auditive hallucinations, and an incoherent thought disorder. While drug abuse was ruled out, he was diagnosed with paranoid schizophrenia and treated with fluphenazine, perphenazine, chlorpromazine, risperidone, and anticholinergics and placed in a supervised home.

Mr. S began experiencing movement disorders in 1994. He was described as clumsy, and he had difficulty walking as well as eating, due to an imbalance and involuntary movement of the tongue, respectively. A diagnosis of neuroacanthocytosis was confirmed in January 1998 following a consultation at our neurogenetic clinic at the Montreal General Hospital. A neurological exam showed that Mr. S had dysarthria, generalized choreiform movements, dystonia of the left leg, postural tremor of the arms, and a diminished sense of vibration. One neurologist suspected executive, attention, and memory dysfunction as well as lack of judgment. However, the neurologist's suppositions were never validated by formal neuropsychological assessment. In July 1999, Mr. S was hospitalized for paranoia and suicidal ideas. He also contracted gambling debts, which was unusual for him. His gambling was considered a possible sign of neuropsychiatric pathology. Mr. S was further treated with haloperidol and olanzapine; still, his behavioral problems were so difficult to manage that he was eventually placed in a nursing home.

Germane to Mr. S's case study is that out of his five siblings, one sister was also affected with neuroacanthocytosis. In his sister's case, the disease presented at age 34, with choreiform movement, personality change with disinhibition, impulsivity, and emotional lability. These behavioral manifestations required psychiatric consultation, and she was treated with haloperidol to control the movement disorder.

Subcortical dementia and changes of personality have been well documented in cases of neuroacanthocytosis. Subcortical dementia, personality change, and movement disorder are pertinent in diagnosing neuroacanthocytosis. Schizophrenia-like presentations, on the other hand, may confound the diagnosis.

Only a few articles referenced in our study discuss psychosis associated with neuroacanthocytosis. Rovito10 described a case that presented with acanthocytosis, which was discovered because of gastrointestinal complaints and psychosis. A Japanese team11 also described a similar association.

We believe that these cases are pertinent for many reasons. First, they underscore the necessity for vigilance in determining secondary causes of psychosis while conducting a neurological exam and careful familial, developmental, and clinical evaluation of all initial psychotic episodes.

Second, such cases emphasize the possible confusion between tardive dyskinesia and a primary movement disorder. They stress the need to investigate all de novo movement disorders in psychotic patients in order to eliminate etiologies other than iatrogenic ones.

Third, one should keep in mind that CK elevations in an agitated psychotic patient are not synonymous with neuroleptic malignant syndrome (NMS) and could be indicative of neuroacanthocytosis. However, the morbidity and mortality associated with NMS should generate immediate treatment response with thorough secondary investigation and differential diagnosis.

Lastly, dopaminergic dysfunction has been described in cases of neuroacanthocytosis. Imagery and pathology analyses have revealed degeneration of the head of the caudate nuclei and putamen,4,7,8 and [18F]-fluorodopa and [11]C-raclopride position emission tomography (PET) tests have showed a dysfunction of dopaminergic pathways, with a preferential loss of nigrostriatal projections.8,12 Dopaminergic mesocortical and mesolimbic dysfunction are at the crossroads of most schizophrenia theories. In addition, we are aware of schizophrenic, drug-naive patients who have symptoms of movement disorders.13 Further studies must demonstrate whether psychosis in neuroacanthocytosis is more prevalent than what can be predicted by epidemiological data.

Psychiatric presentations could represent a differential phenotypic expression that clusters in some families of neuroacanthocytosis, which has been described in Huntington's disease.14 These cases highlight the necessity to reexamine our understanding of the intricate relationships between movement disorders and psychosis, which might reveal new insights in the pathophysiology of psychoses.

Shibasaki H, Sakai T, Nishimura H, et al: Involuntary movements in chorea-acanthocytosis: a comparison with Huntington's chorea. Ann Neurol  1982; 12:311—314
[CrossRef] | [PubMed]
 
Bohlega S, Riley W, Powe J, et al: Neuroacanthocytosis and aprebetalipoproteinemia. Neurology  1998; 50:1912—1914
[PubMed]
 
Sotaniemi KA: Chorea-acanthocytosis. Acta Neurol Scand  1983; 68:53—56
[CrossRef] | [PubMed]
 
Hardie J, Pullon HWH, Harding AE, et al: Neuroacanthocytosis. Brain  1991; 114:13—49
[PubMed]
 
Sakai T, Mawatari S, Iwashita H, et al: Choreoacanthocytosis. Arch Neurol  1981; 38:335—338
[PubMed]
 
Kartsounis LD, Hardie J: The pattern of cognitive impairments in neuroacanthocytosis. Arch Neurol  1996; 53:77—80
[PubMed]
 
Delecluse F, Deleval J, Gérard JM, et al: Frontal impairment and hypoperfusion in neuroacanthocytosis. Arch Neurol  1991; 48:232—234
[PubMed]
 
Rinne JO, Daniel SE, Scaravilli F: The neuropathological features of neuroacanthocytosis. Mov Disord  1994; 9(3):297—304
[CrossRef] | [PubMed]
 
Gross KB, Skrivanek JA, Carlson KC, et al: Familial amyotrophic chorea with acanthocytosis. Arch Neurol  1985; 42:753—756
[PubMed]
 
Rovito DA, Pirone FJ: Acanthocytosis associated with schizophrenia. Am J Psychiatry  1963; 120:182—185
[PubMed]
 
Takahashi Y, Kojima T, Atsumi Y, et al: Case of chorea-acanthocytosis with various psychotic symptoms. Psych Neurol Japanica  1983; 85(8):457—472
 
Dubinsky RM, Hallet M, Levey R, et al: Regional brain glucose metabolism in neuroacanthocytosis. Neurology  1989; 39:1253—1255
[PubMed]
 
Kopala LC. Spontaneous and drug-induced movement disorders in schizophrenia. Acta Psychiatr Scand  1996; 94:12—17
[CrossRef]
 
Folstein SE, Folstein MF: Psychiatric features of Huntington's Disease: recent approaches and findings. Psychol Dev  1983; 2:193—206
 
+

References

Shibasaki H, Sakai T, Nishimura H, et al: Involuntary movements in chorea-acanthocytosis: a comparison with Huntington's chorea. Ann Neurol  1982; 12:311—314
[CrossRef] | [PubMed]
 
Bohlega S, Riley W, Powe J, et al: Neuroacanthocytosis and aprebetalipoproteinemia. Neurology  1998; 50:1912—1914
[PubMed]
 
Sotaniemi KA: Chorea-acanthocytosis. Acta Neurol Scand  1983; 68:53—56
[CrossRef] | [PubMed]
 
Hardie J, Pullon HWH, Harding AE, et al: Neuroacanthocytosis. Brain  1991; 114:13—49
[PubMed]
 
Sakai T, Mawatari S, Iwashita H, et al: Choreoacanthocytosis. Arch Neurol  1981; 38:335—338
[PubMed]
 
Kartsounis LD, Hardie J: The pattern of cognitive impairments in neuroacanthocytosis. Arch Neurol  1996; 53:77—80
[PubMed]
 
Delecluse F, Deleval J, Gérard JM, et al: Frontal impairment and hypoperfusion in neuroacanthocytosis. Arch Neurol  1991; 48:232—234
[PubMed]
 
Rinne JO, Daniel SE, Scaravilli F: The neuropathological features of neuroacanthocytosis. Mov Disord  1994; 9(3):297—304
[CrossRef] | [PubMed]
 
Gross KB, Skrivanek JA, Carlson KC, et al: Familial amyotrophic chorea with acanthocytosis. Arch Neurol  1985; 42:753—756
[PubMed]
 
Rovito DA, Pirone FJ: Acanthocytosis associated with schizophrenia. Am J Psychiatry  1963; 120:182—185
[PubMed]
 
Takahashi Y, Kojima T, Atsumi Y, et al: Case of chorea-acanthocytosis with various psychotic symptoms. Psych Neurol Japanica  1983; 85(8):457—472
 
Dubinsky RM, Hallet M, Levey R, et al: Regional brain glucose metabolism in neuroacanthocytosis. Neurology  1989; 39:1253—1255
[PubMed]
 
Kopala LC. Spontaneous and drug-induced movement disorders in schizophrenia. Acta Psychiatr Scand  1996; 94:12—17
[CrossRef]
 
Folstein SE, Folstein MF: Psychiatric features of Huntington's Disease: recent approaches and findings. Psychol Dev  1983; 2:193—206
 
+
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