Cerebral vasospasm in acute porphyria.

BACKGROUND AND PURPOSE: Porphyrias are a group of inherited metabolic disorders resulting from a specific deficiency along the pathway of haem biosynthesis. A clinical classification distinguishes acute from non-acute porphyrias considering the occurrence of life-threatening neurovisceral attacks, presenting with abdominal pain, neuropsychiatric disturbance and neuropathy. Vasospasm is a very rare complication that can occur in all major types of acute porphyria. METHODS: We describe a porphyric crisis with vasospasm in a woman with previously undiagnosed acute porphyria. Furthermore we performed a systematic review by searching the electronic database Pubmed/MEDLINE for additional data in published studies of vasospasm in acute porphyria. RESULTS: Overall, 9 case reports reporting on 11 patients who suffered vasospasm during an exacerbation of acute porphyria were identified. All of the reported patients were women and the mean age was 29.4 years. When brain MRI was performed, T2-hyperintense lesions, consistent with ischaemic changes, were observed in most patients (10/11, 91%). Although the genetic pathogenesis of the disease is well understood, the precise mechanisms to explain neurologic involvement in acute porphyria remain unclear. CONCLUSION: Acute porphyria is an unusual and rare cause of vasospasm. However, considering porphyria in patients with unexplained cerebral vasospasm, especially in women of childbearing age, is crucial given the severity of possible complications and the available treatment options.

La porfiria: no solo la histeria es una gran simuladora / Porphyria: not only the hysteria is a great imitator

Las porfirias son enfermedades caracterizadas por la acumulación de porfirinas y precursores de porfirina debido a deficiencias enzimáticas en la síntesis del grupo hemo. Esta enfermedad simula una amplia variedad de trastornos, dada la multitud de síntomas con la que se puede presentar, y por lo tanto plantea grandes dificultades diagnósticas. Se presenta un caso en el que la existencia de síntomas psiquiátricos se vio empañada por la presencia de otros síntomas clásicos de la porfiria. Hay un alto riesgo vital en los pacientes afectos de porfiria, tanto por el infradiagnóstico como por la variedad de síntomas que presentan que pueden enmascarar algunos tan severos como una psicosis (AU)

The porphyrias are diseases characterised by accumulation of porphyrins and porphyrin precursors due to enzymatic deficiencies of the haem-synthesis pathaway. It mimics a variety of disorders and thus poses a diagnostic quagmire. A case is reported in which the presence of psychiatric symptoms was masked by the presence of other classic symptoms of porphyria. There is a vital risk in patients with porphyria, due to underdiagnosis presented, as well as the variety of symptoms that arise that may mask some as severe as psychosis (AU)

Entre la locura y el poder: La vida de Jorge III de Inglaterra / Between madness and power: The life of George III of England

En tiempo de las Invasiones Inglesas reinaba en Gran Bretaña Jorge III (1738-1820), singular personaje afectado por crisis demenciales temporarias que lo inhabilitaban para gobernar. El soberano padecía de porfiria, enfermedad metabólica que cursa con brotes de esquizofrenia. Debió superar muchos cambios políticos, la Guerra de los Siete Años y la Guerra de la Independencia de Gales, luego de haber designado primer ministro a Williams Pitt. Después de un ataque muy severo sufrido por el monarca en 1788, el doctor Richard Warren emitió un veredicto decisivo: Rex noster insanita (nuestro rey está loco), refiriéndose a su paciente regio, que murió ciego, sordo y en estado de demencia senil. La dimensión patológica de Jorge III ha sido evaluada por el historiador Vivian Green, profesor de Oxford, quien determinó que más que una tragedia pública, la locura del rey inglés fue una desgracia personal.

At the time of the English Invasions, George III (1738-1820) reigned in Great Britain; a singular character affected by temporary dementia crisis that inhibit him to reign. The King suffered of porphyria, a metabolic disease with frequent outbreaks of schizophrenia. He had to overcome many political changes, the Seven Years' War and the Welsh Independence's War, after appointing Williams Pitt as prime minister. After a very severe attack undergone by the monarch in 1788, doctor Richard Warren issued a decisive verdict: Rex noster insanita (our king is crazy), referring to his regal patient, who died blind, deaf and in a state of senile dementia. The pathological dimension of George III has been evaluated by the historian Vivian Green, an Oxford professor, who determined that more than a public tragedy, the madness of the British king was a personal misfortune.

Neuropsychiatric porphyria in patients with refractory epilepsy: report of three cases.

OBJECTIVES: Although epileptic seizures are an infrequent feature of acute attacks of the neuropsychiatric porphyrias, there are no significant reports of porphyria in chronic epilepsy. This paper attempts to redress the balance. METHODS: Three case reports, including detailed laboratory and molecular diagnostics. RESULTS: Two patients with variegate porphyria and one with acute intermittent porphyria, referred within 1 year to a specialist porphyria service, with a long history of chronic refractory epileptic seizures, are described. CONCLUSIONS: Porphyria may be an aetiological factor in some cases of chronic refractory partial or generalised epilepsy. Porphyria should also be considered if addition of a new anti-epileptic medication causes a major deterioration in the epilepsy.

Anxiety and depression in the acute porphyrias.

A previous study of self-rated psychosocial aspects in patients with acute porphyria found that depression, and particularly anxiety, is more common in porphyria patients than in the general population or general medical outpatient attenders. Nearly half of the sample (46%) reported at least some problem with anxiety and/or depression: anxiety caseness was 26% and depression caseness was 13%. This paper extends our previous observations and investigates further the associations between porphyria and anxiety, depression and general mental health in 90 patients (58 acute intermittent porphyria, 32 variegate porphyria). The findings of this study confirm that anxiety is raised in patients with acute intermittent porphyria and with variegate porphyria, in both males and females, compared to the normative population and, using a series of questionnaires exploring the physical and psychosocial features of anxiety, that this anxiety is experienced as a 'relatively stable personality trait', rather than a 'transitory emotional state' (i.e. intrinsic rather than secondary to the porphyria).

Self-rated psychosocial consequences and quality of life in the acute porphyrias.

A battery of self-report psychosocial measures was mailed to 116 patients who had been referred for clinical management (clinic attenders) or laboratory diagnosis (non-clinic attenders) to the London Supraregional Assay Service Centre for Porphyria over the past decade and who tested positive for porphyria. Usable replies were received from 81 (70%) patients. Our interest focused on the prevalence of psychosocial symptoms in acute porphyrias and the perceived effects of porphyria on quality of life and patient experience. Research questions examined included (i), lifestyle factors; (ii) life events; (iii) mental health; (iv) general health; and (v) perceptions of illness of patients receiving specialist clinical management compared to respondents referred for diagnostic investigations, between patients with latent or manifest symptomology and between patients with different types of porphyria. Patients with porphyria have an impaired quality of life, particularly manifest cases, compared to controls and to diabetic patients. Depression, and particularly anxiety, is more common than in the general population or general medical outpatient attenders. Quality oflife is lower in acute intermittent porphyria (AIP) than in other forms of porphyria and a significant number of patients had major life event consequences, e.g. failure to secure, or loss of, employment, limitation of family size. Patients attending a clinic providing specialist porphyria advice, management and counselling received some perceived lifestyle benefits.

Manifestaciones psiquiátricas en las porfirias / Psychiatric manifestations in porphyrias

Las porfirias son trastornos hereditarios o adquiridos de la biosíntesis del Hem. Las principales manifestaciones clínicas son crisis intermitentes de disfución del sistema nervioso, hipersensibilidad de la piel a la luz solar o ambas. Se ha informado de manifestaciones psiquiátricas en el 24 al 80 por ciento de los casos de porfiria aguda intermitente, siendo las más comunes el delirium y la depresión. Presentamos un caso de porfiria aguda intermitente en el que coinciden las manifestaciones somáticas y psiquiátricas de la enfermedad (AU)

The prooxidant effect of 5-aminolevulinic acid in the brain tissue of rats: implications in neuropsychiatric manifestations in porphyrias.

5-Aminolevulinic acid (ALA), a heme precursor accumulated during the clinical expression of acute intermittent porphyria, lead poisoning, and tyrosinosis, has been hypothesized to act as an endogenous source of oxyradicals. We now report oxidative effects on brain tissue of rats submitted to ALA treatment. Upon acute treatment (40 mg/kg body weight) increased total nonheme iron in the cortex (20%) was observed. After prolonged ALA administration (40 mg/kg body weight on alternate days during 2 weeks), the following indicators of oxidative stress were found to be significantly increased: CuZnSOD activity (67%) in total brain homogenate, total iron (68%) and ferritin (71%) in the cortex, ferritin in striatum (44%), protein carbonyls in homogenate of cerebral cortex (threefold) and 45Ca2+ uptake by cortical synaptosomes (45%). In addition, synaptic membranes prepared from whole brain assayed with the radioligand 3H-muscimol, revealed increased Kd values (twofold) of the high-affinity GABAergic receptor binding and formation of protein carbonyl groups, thiobarbituric acid reactive products, and conjugated dienes. In vitro, ALA produced similar effects upon the high affinity 3H-muscimol binding. No apparent alteration of either dopaminergic or serotonergic [3H]-ligand binding was observed. These results argue in favor of ALA-triggered oxidative stress in brain accompanied by iron metabolism alterations and GABAergic receptor damage, which may be implicated in the neuropsychiatric manifestations of the aforementioned porphyrias.

Porphyria: reexamination of psychiatric implications.

Acute intermittent porphyria mimics a variety of commonly occurring disorders and thus poses a diagnostic quagmire. Psychiatric manifestations include hysteria, anxiety, depression, phobias, psychosis, organic disorders, agitation, delirium, and altered consciousness ranging from somnolence to coma. Some patients develop psychosis similar to schizophrenia. Psychiatric hospitals have a disproportionate number of patients with this disorder as only difficult and resistant patients accumulate there. Presence of photosensitive porphyrins in the urine is diagnostic. When porphyrins are absent, excess of alpha aminolevulinic acid and porphobilinogen are present in the urine. The definitive test is to measure monopyrrole porphobilinogen deaminase in RBCs. This diagnosis should be entertained in the following situations: (a) unexplained leukocytosis; (b) unexplained neuropathy; (c) etiologically obscure neurosis or psychosis; (d) 'idiopathic' seizure disorder; (e) unexplained abdominal pain; (f) conversion hysteria, and (g) susceptibility to stress. Porphyria is important in psychiatry as it may present with only psychiatric symptoms; it may masquerade as a psychosis and the patient may be treated as a schizophrenic person for years; the only manifestation may be histrionic personality disorder which may not receive much attention. Diagnosis is based on a high index of suspicion and appropriate investigation. Various psychotropic drugs exacerbate acute attacks. While it is important not to use the unsafe drugs in porphyric patients, it is also imperative to look for this diagnosis in cases where these drugs produce unprecedented drug reactions.

Varied psychiatric manifestations of acute intermittent porphyria.

Acute Intermittent Porphyria (AIP) is an autosomal dominant metabolic disorder that has various psychiatric manifestations. This is a report of a case who had six brief psychotic episodes of varying nature within a 2-month period. The psychotic manifestations included catatonic stupor, hypomania, and delirium in different episodes. The management aspects of the case have been highlighted.

Acute intermittent porphyria in a children's psychiatric hospital.

Acute intermittent porphyria (AIP) is a rare autosomal disease that presents with gastrointestinal, psychiatric, and neurological symptoms. Bizarre behaviors are common to several illnesses present in a psychiatric setting. Most often these are manifestations of psychotic illness such as schizophrenia or manic-depressive illness, but they can also be seen in cases of organic mental dysfunction and toxic psychotic states. The author describes the disorder and reports on two cases of AIP in children who were initially diagnosed as atypical psychosis in an inpatient children's psychiatric hospital over a 3-year period.