Hyperprolactinemia associated with acute intermittent porphyria

Galactorrhea as the result of hyperprolactinemia has been described in very rare cases associated to acute outbreaks of intermittent acute porphyria (IAP). In our country, any of such cases have been published or analytically documented. We present the case of a patient admitted in our hospital for the study of abdominal pain and galactorrhea, with latter diagnosis of IAP, supported by the assessment of the activity of the enzyme showing a deficit in the red blood cells.     

Transient cortical blindness in gestational hypertension: report of two cases

Transient blindness of cortical origin associated with gestational (pregnancy induced) hypertension is a terrifying and unusual experience in obstetric practice. Two cases encountered in our centre at the University of Ilorin Teaching Hospital (UITH) Ilorin, Nigeria are presented. One case occurred in pregnancy and the other in early puerperium. The two patients were Nigerians. The possible aetiology and pathophysiology of this very rare condition are discussed.     

Pathophysiology and diagnosis of acute intermittent porphyria

Apart from the determination of preporphyrin and porphyrin in the urine recently enzymatic methods entered the diagnostics of the acute intermittent porphyria. Of particular importance is the decrease of activity of the uroporphyrogen-1-synthetase in the manifest disease as well as in the clinically healthy carriers of genes. Since the clinical picture as well as the values of chemical laboratory examinations in the acute intermittent porphyria are extraordinarily variable, a long-term control of diagnostics and therapy is necessary.     

Mortality in patients with acute intermittent porphyria requiring hospitalization: a United States case series

Acute intermittent porphyria (AIP) is a genetic disorder in which patients may have life threatening attacks of neurologic dysfunction. This study examined the prognosis during the past 50 years of patients in the United States who required hospitalization for porphyric attacks. The cumulative survival was determined for 136 patients with AIP who were hospitalized for porphyric attacks between 1940 and 1988. Diagnosis was established on the basis of clinical symptoms, in combination with increased urinary excretion of porphobilinogen. The patient group had an average age of 32 years (range 9 to 75) at diagnosis and consisted of 43 males and 93 females. At follow-up, 19 males (44%) and 31 females (33%) were decreased. The standardized mortality ratio for the 136 patients, compared to an age-matched hypothetical population experiencing USA 1970 Census Death Rates was 3.2, with a 95% confidence interval of 2.4-4.0. Most deaths occurred during the initial porphyric attack (20% of deaths) or a subsequent attack (38% of deaths). Suicide was also common (five deaths). Comparison was made between 50 patients who were diagnosed before 1971, the year in which hematin therapy became available, and 86 patients who were diagnosed afterward. There was improved survival in the latter group, particularly after 10 years from the time of diagnosis, but this did not reach statistical significance. In conclusion, the proportionate increase in mortality due to symptomatic AIP was three-fold compared to the general population during the past 50 years. The major cause of the increased mortality was the porphyric attack itself.     

Acute intermittent porphyria with relapsing acute pancreatitis and unconjugated hyperbilirubinemia without overt hemolysis

A 36-year-old woman was admitted to hospital with a first attack of acute intermittent porphyria. At the same time increased serum levels of amylase and lipase as well as an increased amylase clearance to creatinine clearance ratio were observed, permitting the diagnosis of acute pancreatitis. The etiology of the latter could not be determined. In addition, elevation of indirect bilirubin without evidence of hemolysis was observed Gilbert's syndrome was suspected. 40 weeks after the first episode, a second attack of identical abdominal pain was noted, with elevation of pancreatic enzymes in the serum. There is evidence that acute intermittent porphyria and acute relapsing pancreatitis may have some etiological connection in this patient.     

Propofol and electroconvulsive therapy in a patient at risk from acute intermittent porphyria

Evidence for the involvement of the cranial arterial system in migraine is plentiful, but it is unclear whether the cranial venous system may be involved in the mechanism of migraine pain. Venules are the preferentially involved vessels in the neurogenic inflammation animal model of migraine. The cranial and cerebral veins and sinuses are pain sensitive and receive sensory innervation from the trigeminal nerve. If the veins are involved in migraine pathogenesis, a venous dilatation would presumably be painful. The effect of a short lasting cranial venous dilatation, induced by applying pressure on the internal jugular veins (Queckenstedt's manoeuvre), was therefore compared with a placebo procedure, consisting of an equal pressure applied on to the lateral aspect of the neck. In each procedure pressure was applied for 10 seconds. The study used a single blind, randomised, cross over design, and 20 patients with an acute attack of migraine without aura participated. After each procedure, headache intensity was rated on a standardised five point scale. After Queckenstedt's manoeuvre 40% of the patients reported no change in headache intensity, 25% a worsening, and 35% an improvement of their headache. No significant difference between the headache intensity ratings during Queckenstedt's manoeuvre and the placebo manoeuvre was found (p=0.22). The findings make it unlikely that the cephalic venous system is of major importance in migraine pain mechanisms and, therefore, also less likely that neurogenic inflammation plays a significant part in humans during attacks of migraine without aura.     

Iatrogenically induced cortical blindness associated with leptomeningeal enhancement

Leptomeningeal enhancement is usually infective or neoplastic in origin. We present a case in which a patient received total parenteral nutrition via a catheter unknowingly placed within the right vertebral artery. We postulate that the hyperosmolar nature of the infused solution induced temporary osmotic disruption of the blood-brain barrier, resulting in cortical blindness associated with localized leptomeningeal enhancement.     

Acute intermittent porphyria: report on 17 patients with 49 attacks (author's transl)

In 17 patients (15 women, 2 men) with acute intermittent porphyria in the incidence of 23 clinical symptoms during 49 attacks was calculated. The most frequent symptoms in percentage of attacks were: Red colour of the urine 100%, abdominal pain 92%, tachycardia 88%, hypertension 75%, vomiting 54%, peripheral neuropathy 50%. In 35% of acute attacks a transient normochromic, normocytic anemia developed which is probably due to a disturbance of heme synthesis. Oliguria was found in 25%, azotemia in 12.5% of attacks. 4 patients with an average of 5 preceding acute attacks showed a persistent reduction of renal function during the symptom-free interval, in contrast to 12 patients with an average of 1.7 previous attacks and normal renal function. During the observation period from 1960-1974 3 (= 18%) of the 17 patients died.     

Clinical and laboratory findings concerning at first dietary and afterwards cimetidine treatment of acute intermittent porphyria

Clinical symptoms and laboratory findings were assessed in three women with acute intermittent porphyria. After 15 days of pharmacologic washout and free diet (time 0), the patients were give a well balanced normocaloric diet for 7 days (time 1), followed by 7 days of high carbohydrate normocaloric diet (time 2); on days 15 to 21 (time 3) well balanced normocaloric diet was given, and finally on days 22 to 28 (time 4) to the well balanced normocaloric diet cimetidine (0.4 g twice daily) was added. On days 3, 5, and 7 of times 1-4 the following porphyrin precursors were determined: ALA, PBG, total uroporphyrin, total coproporphyrin, and total porphyrin. At times 1 and 3, high values were found while levels dropped to normal during times 2 and 4. During times 1 and 3, patients complained of headache, insomnia and anxiety; during time 2, all patients complained of anxiety and only one suffered from insomnia. Finally, during time 4, all patients had only slight anxiety. Untoward effects of cimetidine were not observed in any of the patients.     

Diagnosis of acute intermittent porphyria in northern Sweden: an evaluation of mutation analysis and biochemical methods

Pathology of the primary sensory neurons was examined in 7 autopsied patients and 6 biopsied sural nerves from the patients with X-linked recessive bulbospinal neuronopathy (SBMA). Large myelinated fibers in the central rami (L-4 posterior root, L-4, T-7, and C-6 segment of the fasciculus gracilis), and in the peripheral rami (sural nerve) were diminished in a distally accentuated manner, while small myelinated and unmyelinate fibers were well preserved in number. Demylinating process and axonal atrophy was ubiquitous. The diameter frequency histograms of the dorsal root ganglion (DRG) neurons showed a decrease in the number of large diameter neurons and an increase in the number of small diameter neurons without substantial loss of whole number of neurons, which suggested that neuronal size was atrophied. These data suggested central and peripheral distal axonopathy with neuronal atrophy was the process of sensory neuron involvement. Expression of mutant androgen receptor mRNA with elongated CAG repeat in the DRG and sural nerve supported the view that sensory nerve involvement is the primary process in SBMA.     

Sleep and breathing disorders in patients with brain stem lesions

Most information about the structures within the brain stem that modulate respiration and sleep are gathered from animal experiments. Therefore we examined 10 patients several weeks after an infarction of the brain stem by means of polysomnography and tested the chemosensitive drives of respiration. None of these patients complained about symptoms of sleep disordered breathing. In each case polysomnographic measurements and ventilatory response curves revealed pathologic findings. The respiratory response to CO2 was diminished or completely abolished in each patient. In some cases hypoventilation or disturbances of the respiratory rhythmicity could be seen. In several cases missing REM sleep, sleep fragmentation or the reduction of slow wave sleep were observed. The study indicates that on the base of results from animal research the comparison of morphological and pathophysiological data is helpful to gain a better understanding on the coupling of the respiratory system with sleep at the brain stem level as well as on the pathomechanism of sleep related breathing disorder.     

Transient blindness associated with reversible occipital white matter abnormalities: two patients studied by MR, CT, and 18F-FDG PET imaging

We report the case of a patient with mycosis fungoides, stage II B with generalized plaques and ulcerated tumors in a severely reduced general condition, with anemia and extremely poor compliance, who was successfully treated with total-skin electron-beam radiotherapy with a less severe relapse after more than three years.     

Magnetoencephalographic mapping: basic of a new functional risk profile in the selection of patients with cortical brain lesions

OBJECTIVE: Surgical management of cortical lesions adjacent to or within the eloquent cerebral cortex requires a critical risk: benefit analysis of the procedure before intervention. This study introduced a measure of surgical risk, based on preoperative magnetoencephalographic (MEG) sensory and motor mapping, and tested its value in predicting surgical morbidity. METHODS: Forty patients (21 men and 19 women; mean age, 36.5 yr) with cortical lesions (12 arteriovenous malformations and 28 tumors) in the vicinity of the sensorimotor cortex were classified into high-, medium-, or low-risk categories by using the MEG-defined functional risk profile (FRP). This was based on the minimal distance between the lesion margin and the sensory and motor MEG sources, superimposed on a magnetic resonance imaging scan. Case management decisions were based on the MEG mapping-derived FRP in combination with biopsy pathological findings, radiographic findings, and anatomic characteristics of the lesion. A recently developed protocol was used to transform MEG source locations into the stereotactic coordinate system. This procedure provided intraoperative access to MEG data in combination with stereotactic anatomic data displays routinely available on-line during surgery. RESULTS: It was determined that 11 patients diagnosed as having gliomas had high FRPs. The margin of the lesion was less than 4 mm from the nearest MEG dipole or involved the central sulcus directly. A nonoperative approach was used for six patients of this group, based on the MEG mapping-derived FRP. In the group with arteriovenous malformations, 6 of 12 patients with high or medium FRPs underwent nonoperative therapy. The remaining 28 patients, whose lesions showed satisfactory FRPs, underwent uneventful lesion resection, without postoperative neurological deficits. CONCLUSION: Our results suggest that MEG mapping-derived FRPs can serve as powerful tools for use in presurgical planning and during surgery.     

Factor-defined abilities in patients with unilateral brain lesions.

Administered a battery of 4 tests adapted from the structure of intellect model of differential abilities to 72 adults with right and left cerebral lesions and normals. Findings show that both brain-damaged groups exhibited slower response times than normals and that there was a relation between locus of the lesion and performance. However, results do not sufficiently demonstrate the advantage of factor-defined ability tests over tests of global intelligence and question the validity of these factor-defined tests in that they do not distinguish behaviors that are factorially distinct in normal populations. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Axonal excitability and motor propagation velocity of peripheral nerves in patients with acute vascular lesions of the brain

From measurements of maximum and minimum motor nerve propagation velocity and neuronal excitability we conclude that there is a functional loss of motor units and distal nerve "dying back" in persons affected with unilateral acute cerebral vascular lesions. The study also suggests that transynaptic degeneration affects the lower motor neurone function on both sides.     

Prevention of acute intermittent porphyria is the best solution. Most important are early diagnosis and counseling

Recent mapping of acute intermittent porphyria (AIP) in Sweden has confirmed its very high prevalence in northern districts, though about fifty per cent of the gene carriers are to be found in the central and southern parts of the country. More than eighteen different AIP mutations are currently recognised in the Swedish kindreds. One mutations, evidently originating in northern Sweden, is predominant. As AIP is a pharmacogenetic disease, more than 200 substances being currently known to precipitate the neuropsychiatric symptoms, the greatest care is required in prescribing drugs to carriers of genetic predisposition to the disease. Guidelines are provided in the booklet. Drugs contraindicated in acute porphyria (L?kemedel farliga vid akut porfyri), jointly issued by the Swedish Porphyria Association and the Corporation of Swedish Pharmacists (Apoteksbolaget). Where doubt exists, specialists should be consulted since there are a number of factors that may contribute to an adverse reaction. Early diagnosis, preferably before puberty, and counselling are the cornerstones of management, and genetic analysis the diagnostic tool of choice, applicable in most families. In the symptomatic phase, glucose or haem arginate is effective in reversing the metabolic processes responsible for the exacerbation. Recently, the hepatic and late renal manifestations of the disease have been recognised, and early detection of the associated conditions is recommended. This includes monitoring for paraneoplastic prodromes of hepatocellular cancer.     

Imitative response tendencies in patients with frontal brain lesions.

It is widely accepted that patients with frontal lesions have problems inhibiting automatic response tendencies. Whereas inhibition deficits of overlearned responses have been extensively investigated using interference tasks like the Stroop task (J. R. Stroop, 1935), it is controversial whether patients with frontal brain lesions also have problems inhibiting imitative responses. Using an interference paradigm, the present study investigated imitative response tendencies in patients with frontal lesions. In addition, it tested whether patients deficient in the inhibition of imitative responses correspondingly have problems inhibiting overlearned responses. It was found that the group with frontal lesions displayed significantly stronger imitative response tendencies than the group with nonfrontal lesions. Furthermore, it was shown that the inhibition of imitative responses is functionally unrelated to Stroop interference. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Transient monocular blindness and antiphospholipid antibodies in systemic lupus erythematosus

Cation binding to the monovalent cation selective channel, gramicidin A, is shown to induce changes in the dipolar and chemical shift observables from uniformly aligned samples. While these changes could be the result of structural or dynamic changes, they are shown to be primarily induced by through-bond polarizability effects when cations are solvated by the carbonyl oxygens of the peptide backbone. Upon cation binding partial charges are changed throughout the peptide plane, inducing large changes in the 13C1 chemical shifts, smaller changes in the 15N chemical shifts, and even smaller effects for the 15N-13C1 and 15N-2H dipolar interactions. These conclusions are substantiated by characterizing the 15N chemical shift tensors in the presence and absence of cations in fast-frozen lipid bilayer preparations of gramicidin A.