Serum ferritin in children with attention-deficit hyperactivity disorder

To further define a role for iron deficiency in attention-deficit hyperactivity disorder, serum ferritin was included in a battery of laboratory tests obtained in children attending a clinic for attention deficit disorders. In a total of 68 consecutive patients (ages 5-16 years; 54 male, 14 female), the range of serum ferritin levels was a low of 7.7 ng/mL and a high of 150 ng/mL. The mean (+/-S.D.) serum ferritin level in patients with attention-deficit hyperactivity disorder (39.9 +/- 40.6 ng/mL) was not different from that of control subjects. Seventy-four percent of patients had serum ferritin levels below 50 ng/mL; 44% were below 30 ng/mL; and 18% below 20 ng/mL. None had evidence of iron deficiency anemia. A comparison of the clinical characteristics of the 12 patients with the lowest serum ferritin levels (<20 ng/mL) and 12 with the highest levels (>60 ng/mL) disclosed no significant difference in severity or frequency of attention-deficit hyperactivity disorder and comorbid symptoms or response to medications. In this patient cohort, a causative role for low serum ferritin in attention-deficit hyperactivity disorder has not been confirmed.     

Hypocretin (orexin) and melatonin values in a narcoleptic-like sleep disorder after pinealectomy

Narcolepsy secondary to other neurologic processes has been recently associated with hypocretin (orexin) deficiency. We present a patient who developed a narcoleptic-like sleep disorder after receiving treatment for a choroid plexus carcinoma of the pineal gland. She underwent a pinealectomy, chemotherapy, and radiation treatment. The primary features of this condition were excessive daytime sleepiness, sleep paralysis and hypnagogic hallucinations. Increased percentage of rapid eye movement (REM) sleep and sleep onset REM periods were seen during the multiple sleep latency test. Circadian rhythmicity was preserved for melatonin and cortisol. She was negative for human leukocyte antigen DQB1*0602 and had a detectable cerebrospinal fluid hypocretin level (518 pg/ml). We emphasize that the narcoleptic-like disorder likely resulted from the surgical intervention or radiation therapy. Her symptoms are caused by an unknown mechanism unrelated to hypocretin depletion which merits more research.     

Severe methylenetetrahydrofolate reductase (MTHFR) deficiency: a case report of nonclassical homocystinuria

Severe methylenetetrahydrofolate reductase deficiency is an autosomal recessive metabolic disorder of folate metabolism causing elevated plasma homocysteine levels and homocystinuria (MIM 236250). A developmentally delayed 10-year-old girl presented with symptoms of progressive ataxia, dysarthria, tremor, mental status changes, and white-matter changes on magnetic resonance imaging. These changes occurred during a 3- to 4-month time period, with an acceleration of symptoms during 2 to 3 weeks. The patient was found to have extremely high serum homocysteine and low-normal serum methionine. She received treatment with vitamin B12, folate, betaine, multivitamins, and aspirin, with subsequent improvement of her symptoms and reduction in her serum homocysteine level. This case emphasizes the need to include homocystinuria in the differential diagnosis of children with acute/subacute neurological changes, particularly in the context of developmental delay.     

Attention deficits and autistic spectrum problems in children exposed to alcohol during gestation: a follow-up study

Children born to mothers who had abused alcohol throughout pregnancy had severe behavioural and intellectual problems which remained at age 11 to 14 years. Of 24 children examined, 10 had attention deficit hyperactivity disorder (ADHD) with or without developmental coordination disorder, two had Asperger syndrome, and one had an autistic-like condition not meeting the criteria for Asperger syndrome. Six of these 24 attended special schools for the mentally retarded and a further 11 were given special education, leaving only seven attending regular schools without any type of support. The children had difficulties in mathematics, logical conclusions, visual perception, spatial relations, short-term memory, and attention. Sixteen children lived in foster homes. There was a clear correlation between the occurrence and severity of the neuropsychiatric disorder and the degree of alcohol exposure in utero.     

Mirror writing resulting from an egocentric representation disorder: a case report

Buchwald (1878 ) used the term 'mirror writing' to indicate writing in the reverse direction to what is normal in a particular language and in which the individual letters are also reversed. Cases of healthy individuals (i.e., Leonardo da Vinci and Lewis Carroll) as well as brain-damaged patients have been described in the literature. Here, we report the case of PM, a 70-year-old right-handed woman who showed right hemiplegia and mirror writing following a stroke in the left lenticular nucleus and internal capsulae. PM underwent a complete neuropsychological evaluation, which included copying, dictation and spontaneous writing in both hemispaces with both hands. She was also tested for topographical disorientation, visuo-spatial disorders and body schema deficits. We observed isolated mirror writing only when PM wrote with the left hand, without differences between hemispaces. She also showed a left-right disorientation, a body topological map disorder and an egocentric misrepresentation. The presence of mirror writing not confined to one hemispace and the co-presence of executive function disorders, as well as anosognosia, suggests damage to our patient's sub-cortical frontal network. As no previous interpretation fits with PM's symptoms, we hypothesize that mirror writing resulted from damage to her egocentric frame of reference. This hypothesis allows us to interpret the patient's array of disorders, including mirror writing, body topological map disorder, left-right confusion and egocentric representation.     

3-methylcrotonyl-CoA carboxylase deficiency and severe multiple sclerosis

This report describes a female with isolated 3-methylcrotonyl-CoA carboxylase deficiency. She had a mild Reye-like episode, loss of scalp hair, psychomotor retardation, and an attention-deficit hyperactivity disorder. The diagnosis was made at 13 years of age when she developed relapsing remitting multiple sclerosis with a malignant course. Treatment with steroids had initially a good therapeutic effect on the relapses. The response to interferon beta-1a treatment was poor. On mitoxantrone treatment there was a considerable neurologic recovery.     

Inborn errors of creatine metabolism and epilepsy: clinical features,diagnosis, and treatment

Creatine metabolism disorders have so far been described at the level of two synthetic steps, guanidinoacetate N-methyltransferase and arginine:glycine amidinotransferase, and at the level of the creatine transporter 1. Guanidinoacetate N-methyltransferase and arginine:glycine amidinotransferase deficiency respond positively to substitutive treatment with creatine monohydrate. Guanidinoacetate N-methyltransferase deficiency results in a severe neurologic disease (age of onset 3 months to 2 years) characterized by developmental arrest, neurologic deterioration, movement disorders, mental retardation, autistic-like behavior, and epilepsy. Severe early-onset epilepsy with pleomorphic seizures is a key symptom of this disorder. Data suggest that in patients with guanidinoacetate N-methyltransferase deficiency, epilepsy and associated electroencephalographic abnormalities are more responsive to creatine supplementation than to conventional antiepilepsy drugs. Arginine:glycine amidinotransferase and creatine transporter 1 mainly present with mental retardation and severe language disorder. All cases of creatine disorders reported to date have been detected by brain proton magnetic resonance spectroscopy, an expensive technique not routinely used in pediatric neurology. A potential diagnostic strategy to select patients for evaluation using proton magnetic resonance spectroscopy is proposed in this review.     

Psychiatric manifestations of vitamin B12 deficiency: a case report

Psychiatric manifestations are frequently associated with pernicious anemia including depression, mania, psychosis, dementia. We report a case of a patient with vitamin B12 deficiency, who has presented severe depression with delusion and Capgras' syndrome, delusion with lability of mood and hypomania successively, during a period of two Months. Case report - Mme V., a 64-Year-old woman, was admitted to the hospital because of confusion. She had no history of psychiatric problems. She had history of diabetes, hypertension and femoral prosthesis. The red blood count revealed a normocytosis with anemia (hemoglobin=11,4 g/dl). At admission she was uncooperative, disoriented in time and presented memory and attention impairment and sleep disorders. She seemed sad and older than her real age. Facial expression and spontaneous movements were reduced, her speech and movements were very slow. She had depressed mood, guilt complex, incurability and devaluation impressions. She had a Capgras' syndrome and delusion of persecution. Her neurologic examination, cerebral scanner and EEG were postponed because of uncooperation. Further investigations confirmed anemia (hemoglobin=11,4 g/dl) and revealed vitamin B12 deficiency (52 pmol/l) and normal folate level. Antibodies to parietal cells were positive in the serum and antibodies to intrinsic factor were negative. An iron deficiency was associated (serum iron=7 micromol/l; serum ferritin concentration=24 mg/l; serum transferrin concentration=3,16 g/l). This association explained normocytocis anemia. Thyroid function, hepatic and renal tests, glycemia, TP, TCA, VS, VDRL-TPHA were normal. Vitamin B12 replacement therapy was started with hydroxycobalamin 1 000 ng/day im for 10 days and iron replacement therapy. Her mental state improved dramatically within a few days. After one week of treatment the only remaining symptoms were lability of mood, delusion of persecution, Capgras' syndrome but disappeared totally 9 days after the beginning of the treatment. A neurologic examination was possible because of cooperation. All the tendon reflexes of inferior members were absent. The plantars were in flexion and there was a left inferior member hypoesthesia. The cerebral scan and EEG were normal. Fundic biopsy, realized by fibroscopy, revealed fundic atrophia and intestinal metaplasia compatible with Biermers' disease. The iron deficiency exploration concluded diet deficiency. Mme V. appeared euphoric, her speech was very rapid with play on words and overactivity. This hypomania state totally disappeared 3 days after. Six Months after her hospitalisation, she presented an hypothyroidism (TSH=3,780; T3=1,35; T4=1,08). A thyroid hormones replacement was started and she continued to receive Monthly B12 replacement. Discussion - This case report illustrates psychiatric manifestations of Biermers' disease. The clinical arguments in favour are: white woman, more than 60 Years old, no history of psychiatric problems, atypical symptoms (confusional state with psychiatric symptoms), fluctuation of symptoms (severe depression with confusional state, delusion of persecution and Capgras' syndrome; delusion with lability of mood and hypomania), dramatic improvement after 9 days of vitamin B12 replacement therapy. The biological arguments are: anemia, vitamin B12 deficiency, normal folate level, atrophia and fundic metaplasia, positive antibodies to parietal cells in the serum, association between Biermers' disease and autoimmune disease (Haschimoto thyroidite). Psychiatric manifestations can occur in the presence of low serum B12 levels but in the absence of the other well recognized neurological and haematological abnormalities of pernicious anemia. Mental or psychological changes may precede haematological signs by Months or Years. They can be the initial symptoms or the only ones. Verbank et al. described the case of a patient with vitamin B12 deficiency in whom hypomania, paranoia and depression had been successively presented during a period of 5 Years before anemia have been developed. The case of Mme V. is similar in the succession of severe depression with delusion of persecution and Capgras' syndrome, delusion with lability of mood and hypomania, during a period of two Months. This report seems to be the first one of a sequence of several psychiatric states with pernicious anemia during a period of two Months with normocytosis anemia. To illustrate this illness we reviewed the literature regarding psychopathology associated with B12 deficiency. The most common psychiatric symptoms were depression, mania, psychotic symptoms, cognitive impairment and obsessive compulsive disorder. The neuropsychiatric severity by vitamin B12 deficiency and the therapeutic efficacy depends on the duration of signs and symptoms. Conclusion - We recommend consideration of B12 deficiency and serum B12 determinations in all the patients with organic mental disorders, atypical psychiatric symptoms and fluctuation of symptomatology. B12 levels should be evaluated with treatment resistant depressive disorders, dementia, psychosis or risk factors for malnutrition such as alcoholism or advancing age associated with neurological symptoms, anemia, malabsorption, gastrointestinal surgery, parasite infestation or strict vegetarian diet. In first intention, B12 deficiency should be researched by serum B12 determination (normal 200-950 pg/ml). Studies of methylmalonic acid and homocysteine showed that they are very sensitive functional indicators of cobalamin status especially when other evidence of cobalamin (B12) deficiency was equivocal. Measurement of methylmalonic acid (normal 73-271 nmol/l) and homocysteine (normal 5,4-13,9 micromol/l) should not replace the measurement of serum cobalamin.     

Is there a comorbid relationship between hyperactivity and emotional psychopathology?

Some of the early literature implied that emotional disorders were almost incompatible with hyperactivity in childhood. The paper addresses this issue using a large epidemiological data base — of two cohorts of 7– & 8-year-old and 11– & 12-year-old children from the North of England. There are two themes, first, the paper reports on the prevalence of emotional symptoms and disorder among hyperactive children. Second, it explores co-occurrence of hyperactivity and emotional psychopathology according to whether the hyperactivity is situational or pervasive and according to the age of the child. Hyperactivity proved to have an association with emotional symptoms and disorder at both ages but the links with disorder were most prominent among the older children. Among our high risk or maladjusted samples the strongest links were with home-based situational hyperactivity. However, among the general population cohort, emotional disorder proved to be a function of pervasiveness of hyperactivity and older age.     

Can stimulant rebound mimic pediatric bipolar disorder?

The authors describe the case of a 7-year-old girl diagnosed with attention deficit hyperactivity disorder (ADHD) who, following an unsuccessful trial of stimulant medication and subsequent mood symptoms, was diagnosed with bipolar disorder. Following a comprehensive, multidisciplinary assessment, and withdrawal of her complex medication regimen, she was rediagnosed with ADHD. She displayed a positive response to behavioral parent training and pharmacological treatment with a long-acting stimulant. The case illustrates the benefits of a comprehensive, multidisciplinary evaluation and multimodal treatment. Her dramatic response to the long-acting stimulant suggests that many of her affective symptoms were due to stimulant "rebound" versus bipolar disorder. This case highlights the complexities of differentiating severe ADHD from bipolar disorder and suggests that stimulant rebound and other iatrogenic effects should be considered during the differential diagnostic process as potential mimics of bipolar disorder.     

Adolescent attention deficit hyperactivity disorder and susceptibility to psychosis in adulthood: a review of the literature and a phenomenological case report

Aim: In contrast to affective disorders, some forms of personality disorders and drug addiction, schizophrenia is commonly not considered to be a sequela of attention deficit hyperactivity disorder. However, attention deficit hyperactivity disorder and the prodromal stages of schizophrenia spectrum disorders do exhibit a number of common central features. To facilitate the early treatment of schizophrenic symptoms, the detection of discrete and subtle alterations in the prodromal stages of incipient psychoses is particularly important. Methods: We review the literature on the prodromal symptoms of psychosis and present a case report, in which a phenomenological approach was used to identify subtle alterations linked to anomalous self‐experience. Results: Using the Examination of Anomalous Self‐Experience symptom checklist, the case report presented here reveals attention deficit hyperactivity disorder symptoms in adolescence as a precursor state of psychosis in adulthood. Conclusions: The characteristics of this schizophrenia spectrum disorder case and its time course are derived from the specific distribution pattern of Examination of Anomalous Self‐Experience items. When treating adolescent attention deficit hyperactivity disorder patients, the rare possibility of the development of schizophrenia spectrum disorder from attention deficit hyperactivity disorder like symptoms should be kept in mind.     

Relationship of psychotic symptom clusters in schizophrenia to neuroleptic treatment and growth hormone response to apomorphine

The authors propose an alternative model for relating clinically rated psychotic symptoms to biological measures in schizophrenic patients. They suggest that clinical presentation in schizophrenic patients comprises at least four distinct psychotic symptom clusters and that at most one or two of the symptom clusters are closely associated with central dopamine (DA) activity as measured by growth hormone (GH) response to apomorphine. Factor and cluster analytic techniques both identified the same four psychotic symptom clusters, three of which were similar to the major subtypes of schizophrenia: paranoid delusions (paranoid type), thought disorder (disorganized type), and catatonia (catatonic type). The fourth psychotic symptom cluster was auditory hallucinations, a prominent clinical feature of schizophrenia. The authors compared clinical symptom cluster scores to apomorphine-induced GH response by creating a new data set containing the output of the factor analysis of each patient's symptoms and GH response, and performing regression modeling of the patient's symptom cluster scores on GH response. Patients with elevated thought disorder cluster scores also had elevated GH responses to apomorphine, suggesting an association between thought disorder and central DA receptor supersensitivity. A fixed-dose neuroleptic trial showed that thought disorder and auditory hallucinations respond rapidly to treatment with a DA receptor blocker (haloperidol), while no significant effect on other symptom cluster scores occurred during the initial 2 weeks of treatment. These data suggest that two of the identified symptom clusters, thought disorder and auditory hallucinations, may be preferentially associated with central DA hyperactivity.     

Neuropsychiatric Assessmenit of Children with Autism: A Population-Based Study

Thirty-five children with autistic disorder and 17 with autistic-like conditions underwent an exhaustive neurobiological evaluation, and the findings were contrasted with those obtained from various comparison groups. Almost 90 per cent of the children with autistic disorder and autistic-like conditions had major indications of brain damage or dysfunction. Some of those who did not show such abnormalities had a first-degree relative with Asperger syndrome. The rate of abnormality was similar to that of severely mentally retarded children, but in excess of that of normal children. Within the autism group, abnormality rate did not correlate with degree of mental retardation. It is concluded that autism has multiple biological aetiologies and that autistic symptoms in a child should always prompt a thorough medical/neurobiological evaluation.     

Reversible choreoathetosis associated with lithium intoxication]

Several reports have been published in the literature of choreoathetosis associated with lithium intoxication, but little is known about choreoathetosis without concurrent antipsychotic treatment. We report a 65-year-old woman with lithium intoxication whose choreoathetosis completely recovered without sequela following decrease of her serum lithium level. She had been treated elsewhere for bipolar II disorder and also for hypertension, chronic hepatitis type C and diabetes mellitus. As she became hypomanic, lithium carbonate at 600 mg/day was commenced, which was increased to 1200 mg/day due to unfavorable therapeutic response. She began to manifest disorientation and abnormal involuntary movement and was therefore referred to our Department of Psychiatry. Her clinical symptoms at admission included consciousness disturbance with marked bilateral symmetrical slow-wave activity in her EEG and choreoathetosis was observed in her face and upper and lower extremities. Cerebellar symptoms were minimal with only mild ataxic gait and finger-to-nose test did not show dysmetria or intention tremor. Her serum lithium level was 3.52 mEq/L, which was clearly in the toxic range. She demonstrated no metabolic abnormalities including hyperglycemia, and was diagnosed with lithium intoxication and treated with water loading and mannitol for forced diuresis. On the 14th day after admission her consciousness disturbance and choreoathetosis resolved, but EEG abnormalities still persisted. On the 23rd day after admission, she was discharged with clinical remission and normal EEG background activity. Although she developed mild renal dysfunction, hemodialysis was not indicated. Hypersensitivity of dopamine receptor in the nigrostriatal pathways may contribute to choreoathetosis in association with the patient's vulnerability. Choreoathetosis can be a sign of lithium intoxication and prompt treatment is required following careful differential diagnosis.     

Inhibitory motor control in children with attention-deficit/hyperactivity disorder: event-related potentials in the stop-signal paradigm.

BACKGROUND: The aim of the study was to investigate the inhibitory control of an ongoing motor response and to identify underlying neural deficiencies, manifested in event-related potentials, that cause poorer inhibitory performance in children with attention-deficit/hyperactivity disorder. METHODS: A stop-signal paradigm with a primary visual task and auditory stop signal was used to compare performance in 13 children with attention-deficit/hyperactivity disorder and 13 control children, while event-related potentials were recorded simultaneously. RESULTS: Children with attention-deficit/hyperactivity disorder showed poorer inhibitory performance through a slower inhibitory process. Inhibitory processing of auditory stop signals was marked by a frontal N2 component that was reduced in the attention-deficit/hyperactivity disorder group relative to controls. A central positive component (P3) was associated with the success of inhibiting a response, but there were no group differences in its amplitude or latency. CONCLUSIONS: Findings support the hypothesis of deficient inhibitory control in children with attention-deficit/hyperactivity disorder. Slower inhibitory processing appears to be due to a specific neural deficiency that manifests in the processing of the stop signal as attenuated negativity in the N2 latency range.     

Socioeconomic status as a moderator of ADHD treatment outcomes

OBJECTIVE: To explore whether socioeconomic status (SES) variables moderate treatment response of attention-deficit/hyperactivity disorder (ADHD) to medication management (MedMgt), behavioral treatment (Beh), combined intervention (Comb), and routine community care (CC). METHOD: The MTA Cooperative Group's intent-to-treat (ITT) analyses were repeated, covarying for composite Hollingshead SES, education, occupation, income, and marital status. RESULTS: Individual SES variables were more informative than the composite Hollingshead Index. Treatment response of children from less educated households paralleled ITT outcomes: no significant difference was found between Comb and MedMgt (both better than Beh and CC) for core ADHD symptoms. However, children from more educated families showed superior reduction of ADHD symptoms with Comb. For oppositional-aggressive symptoms, children from blue-collar, lower SES households benefited most from Comb, whereas those from white-collar, higher SES homes generally showed no differential treatment response. Household income and marital status failed to influence outcomes. Controlling for treatment attendance attenuated the moderating effects of the SES variables only for MedMgt. CONCLUSIONS: Investigators are encouraged to use independent SES variables for maximal explanation of SES effects. Clinicians should prioritize target symptoms and consider the mediating role of treatment adherence when determining an ADHD patient's optimal intervention plan.     

Lifespan attention deficit/hyperactivity disorder and borderline personality disorder symptoms in female patients: a latent class approach

Attention-deficit/hyperactivity disorder (ADHD) and borderline personality disorder (BPD) are frequently comorbid. To contribute to a better understanding of the associations regularly found between ADHD and BPD, on the one hand, and the developmental pathways for these disorders, on the other hand, latent class analyses (LCA) were undertaken to identify classes differing in profiles of childhood symptoms of ADHD and adult symptoms of ADHD and BPD. Diagnostic interviews with 103 female outpatients meeting the criteria for ADHD and/or BPD were used to assess current DSM-IV symptoms; childhood symptoms of ADHD were assessed in parent interviews. The latent classes were examined in relation to the DSM-IV conceptualizations of ADHD and BPD. And relations between childhood and adult classes were examined to hypothesize about developmental trajectories. LCA revealed an optimal solution with four distinct symptom profiles: only ADHD symptoms; BPD symptoms and only ADHD symptoms of hyperactivity; BPD symptoms and ADHD symptoms of inattention and hyperactivity; BPD symptoms and ADHD symptoms of inattention, hyperactivity and impulsivity. All patients with BPD had some ADHD symptoms in both adulthood and childhood. Hyperactivity was least discriminative of adult classes. Adult hyperactivity was not always preceded by childhood hyperactivity; some cases of comorbid ADHD and BPD symptoms were not preceded by significant childhood ADHD symptoms; and some cases of predominantly BPD symptoms could be traced back to combined symptoms of ADHD in childhood. The results underline the importance of taking ADHD diagnoses into account with BPD. ADHD classification subtypes may not be permanent over time, and different developmental pathways to adult ADHD and BPD should therefore be investigated.     

Slovenian Families With Children With Attention-Deficit/Hyperactivity Disorder: Interpersonal Relations,Parents’ Attention-Deficit/Hyperactivity Disorder Symptoms and Implications for Family Therapy

We aimed to assess interpersonal relationships within Slovenian families with a child diagnosed with attention-deficit/hyperactivity disorder (proband) as compared to control families. The current study evaluated parents’ retrospective assessment of attention-deficit/hyperactivity disorder symptoms in childhood in both groups and possible predictive factors for the occurrence of attention-deficit/hyperactivity disorder in children. The proband parents experienced more difficulties in interpersonal relations, more often related to attention-deficit/hyperactivity disorder symptoms during their childhood and the proband children blamed themselves for marital conflict to a greater extent. The general functioning of families and parents’ attention-deficit/hyperactivity disorder symptoms in their childhood are the most significant predictive factors for the occurrence of the disorder in children. These findings stressed the appropriateness of family therapy focused on interpersonal relationships in families with attention-deficit/hyperactivity disorder children.     

Adeverse Effects of Trimethoprim-sulfamethoxazole in a Child with Dihydropteridine Reductase Deficiency

A child with dihydropteridine reductase (DHPR) deficiency developed signs of dopamine insufficiency after being given trimethoprim-sulfamethoxazole (TMP-SMX). She recovered function after the antibiotic was stopped, which suggests that it adversely influenced dopamine metabolism in the CNS. The authors speculate that TMP, a dihydrofolate reductase inhibitor, was the major cause of the patient's deterioration, and suggest that it and other dihydrofolate inhibitors, notably methotrexate, are contra-indicated for patients with DHPR deficiency.     

Clinical features of carbamyl phosphate synthetase-I deficiency in an adult

Carbamyl phosphate synthetase-I (CPS-I) catalyzes the first reaction required for the conversion of ammonia to urea through the urea cycle. Severe CPS-I deficiency causes marked hyperammonemia with encephalopathy in infancy and usually results in death within the first few months of life. We describe a 33-year-old woman whose CPS-I activity is less than 5% of normal. She has had mild, intermittent symptoms throughout life but has never experienced severe encephalopathy. Although mildly retarded, she has no major neurological deficits. Therapy with a low-protein diet, lactulose, and sodium benzoate has prevented recurrence of hyperammonemia and symptoms. Cranial computed tomographic scans demonstrate prominent lucency of cerebral white matter, and cerebral evoked potential recordings indicate slowed central conduction. These findings suggest that the metabolic disturbances in this patient may have adversely affected central myelin formation or maintenance. This woman represents, to our knowledge, the oldest reported patient with CPS-I deficiency, and the case illustrates the need to consider urea cycle disorders in the differential diagnosis of intermittent neurological symptoms regardless of the patient's age.