Psychosomatics 47:527-528, November-December 2006
doi: 10.1176/appi.psy.47.6.527
© 2006 Academy of Psychosomatic Medicine
Fatal Familial Insomnia
Vanessa Sanchez Gistau, M.D.,
Luis Pintor, M.D.,
Silvia Matrai, M.D., and
Albert Saiz, M.D.
Received November 24, 2005; revised December 23, 2005; accepted January 13, 2006. From the Dept. of Psychiatry, Hospital Clinico de Barcelona; Barcelona, Spain. Send correspondence and reprint requests to Dr. Pintor, Dept. of Psychiatry, Hospital Clinico de Barcelona; Barcelona, Spain. e-mail: lpintor{at}clinic.ub.es
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INTRODUCTION
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Fatal familial insomnia (FFI) is a prion disease first described in 1986.1 The main characteristics include insomnia, dysautonomia, and motor signs.
In 1992,2,3 an autosomal-dominant inherited disease was proposed, consisting of a GAC-to-AAC mutation at codon 178 of the PRNP gene, causing substitution of asparagine for aspartic acid. The change in only one amino acid produces selective degeneration of anterior and dorsomedial thalamic nuclei. As in the case we describe below, psychiatric symptoms may indicate the onset of various diseases. Coordination among clinicians of different specialties and a multidisciplinary approach are necessary to make an accurate diagnosis.
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Case Report
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A 46-year-old woman with no past psychiatric or medical history was admitted to the Psychiatric Inpatient Unit of the Hospital Clinic, Barcelona, to confirm a diagnosis of depressive syndrome and progressive cognitive dysfunction. The family reported that two brothers were receiving pharmacological treatment for major depression, and her father had died at the age of 68 years from a non-specific dementia. They could not give us more information about the father’s psychiatric history because old differences had set them at odds.
Ten months before the admission, she had complained of difficulties with concentration, sleeplessness, hypo-orexia, apathy, anergy, anhedonia, and feeling useless and disabled. She was diagnosed with a major depressive episode and was started on treatment with 150 mg/day of clomipramine and 1.5 mg/day of alprazolam, achieving partial remission of symptoms. During the next months, she experienced memory decline and showed confabulations; vivid nightmares and agitation were observed at night. The findings of neurological and physical examinations were normal. The EEG performed 1 month before admission had showed "diffuse mild slowing."
At admission, she presented significant weight loss, diaphoresis, slight pyrexia, hypertension, tachycardia, and difficulty in micturition. She was disoriented and somnolent, with slowed thinking and depressed mood. The neurological examination revealed low-volume voice, transient diplopia, myoclonic movements of the extremities, and ataxic gait. Pyramidal signs were absent, and neuropsychological tests showed subcortical abnormalities.
The findings of all laboratory blood and urine tests, chest radiograph, and conventional neuroimaging were normal. The 14-3-3 protein was not detected in cerebrospinal fluid. The EEG showed mild slowing, without periodic or pseudoperiodic activities.
Psychopharmacological treatment was discontinued during admission. During the day, the patient showed physical and cognitive impairment; she was sleepy all day, with nocturnal apneas, bizarre behavior, and oneiric automatisms.
Non-specific symptoms and complementary tests, as well as a meticulous completion of personal and family clinical history permitted us to reach a diagnosis. Because the genealogic tree showed a pattern of deaths at relatively young ages, with a rapid course and unknown or unestablished cause, we contacted the neurologist at our hospital who specializes in genetically transmitted diseases, and he determined that the father had been treated in another hospital and had died from a prion disease called fatal familial insomnia (FFI).
Specific study of the disease yielded the following results: the dysautonomia tests demonstrated a vegetative and hormonal dysregulation of circadian cycle, and polysomnographic recordings confirmed global alteration of the sleep–wake cycle and electroencephalographic disorganization of sleep. The genetic study confirmed the mutation causing the illness. The patient died 3 months later.
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Discussion
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FFI is an uncommon disease with non-specific initial symptoms,4 such as motor abnormalities, weight loss, anergy, fatigue, insomnia, and loss of interest. Prion diseases, such as FFI, must be considered as differential diagnoses when a young patient presents with nonspecific affective symptoms and a rapid, progressive cognitive decline.
In FFI, the main complementary tests often do not provide conclusive data. Routine laboratory parameters, structural neuroimaging, and CSF findings are typically normal. EEG is usually normal at the beginning, and becomes progressively slower, with alpha-rhythm diminution wakefulness. Neuropsychological impairments first appear essentially in attention, progressing to memory deficits and impairment of frontal-lobe functions, with preserved general intelligence.
The clinical history of the patient is the main indication for performing complementary tests. In our case, family history was the key factor in the decision to perform specific tests to establish the diagnosis. Polysomnography confirmed the disruption of the normal sleep–wake cycle as the core clinical feature, and genetic study confirmed the mutation.
Families are not always aware of their members’ pathologies; therefore it is especially important not to underestimate any familial or clinical-history fact when investigating a disease with rapid progression and nonspecific features. The information provided by the patient’s history often might be a clue for diagnosis and prognosis; thus, clinicians should not neglect one of the main diagnostic tools, the clinical and family history.
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REFERENCES
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- Lugaresi E, Medori R, Montagna P, et al: Fatal familial insomnia and dysautonomia with selective degeneration of thalamic nuclei. N Engl J Med 1986; 315:997–1003[Medline]
- Gallassi R, Morreale A, Montagna P, et al: Fatal familial insomnia: neuropsychological study of a disease with thalamic degeneration. Cortex 1992; 28:175–187[Medline]
- Medori R, Tritschler H-J, LeBlanc A, et al: Fatal familial insomnia, a prion disease with mutation at codon 178 of the protein gene. N Engl J Med 1992; 336:444–449[CrossRef]
- Collins S, McLean CA, Masters CL: Gerstmann-Straussler-Scheiker syndrome, fatal familial insomnia, and kuru: a review of the less-common human transmissible spongiform encephalopathies. J Clin Neurosci 2001; 8:387–397[CrossRef][Medline]
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INTRODUCTION
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