Josep Ris

Proton magnetic resonance spectroscopy pattern of progressive multifocal leukoencephalopathy in AIDS

The objective was to determine whether the use of intermediate echo times (135 ms) in proton magnetic resonance spectroscopy (1H-MRS) detects a homogenous pattern in progressive multifocal leukoencephalopathy (PML) in HIV-1 infected people, and to confirm the results of previous studies.  Six patients infected with HIV-1, with PML established by biopsy, and six healthy age and sex matched volunteers were evaluated to define their spectroscopic pattern. 1H-MRS spectra performed at 1.5 T were obtained with the STEAM sequence: TE/TM/TR, 20 ms/13.7 ms/2000 ms; 2500 Hz, size 2048 points, 256 acquisitions (STEAM-20) and with the PRESS sequence; TE/TR, 135 ms/2000 ms; 2500 Hz, size 2048 points, 256 acquisitions (PRESS-135). A single voxel was placed on the lesions and on the parieto-occipital white matter of controls. The peaks of N-acetylaspartate (NAA), choline (Cho), myoinositol (mI), lactate, and lipids were considered, and the results were expressed using creatine as reference.  Spectra of PML lesions were characterised by significantly reduced NAA, lactate presence, and by significantly increased Cho and lipids compared with control group values.  These results indicate that 1H-MRS detects a homogenous pattern in PML lesions. Recent studies, together with this, suggest that 1H-MRS may help in the diagnostic approach to patients with suspected PML lesions associated with AIDS.

99mTc-HMPAO SPET: a method to study visual loss in cryptococcal meningitis.

Visual loss, in the absence of direct ocular involvement, is an uncommon but severe complication of cryptococcal meningitis in patients with AIDS (1). To our knowledge, the use of TcHMPAO SPET (Tc-hexamethylpropylene amine oxime single photon emission tomography) for the study of visual loss in cryptococcal meningitis has not been previously reported. We report the use of this method in a 28-yearold HIV-infected woman with a severe cryptococcal meningitis who presented progressive visual loss, with ®nal visual acuity of no light perception in both eyes, pupils symmetrically sluggish to light and normal fundus exam. Tc-HMPAO SPET, showed a slight decrease in the supratentorial cerebral blood ̄ow and hypoperfusion of bilateral occipital and left temporal lobes (Fig. 1). Then, MRI did not show lesions in visual pathways, and evoked potentials were unrecordable in both eyes. One month later visual loss persisted; fundus exam remained normal and MRI showed bilateral lower-signal of optic nerves in a plane. Nine months later fundoscopy showed bilateral optic atrophy. Tc-HMPAO SPET has been used to determine changes in cerebral blood ̄ow. Particularly in the striate cortex, changes in regional cerebral perfusion have been related to visual stimulation, and Tc-HMPAO SPET has been proved as a successful method of diagnosis in cortical blindness (2). On the other hand, in cryptococcal meningitis only few case-reports have showed changes in cerebral blood ̄ow by SPECT, like increased perfusion in meningoencephalitis (3) and focal hypoperfusion in cryptococcomas (4). Although SPECT has not been previously used for the study of visual alterations in cryptococcal meningitis, it should be considered. In this disorder anatomical imaging studies are usually not conclusive. CT is useful to rule out focal lesions (1, 4) and, despite that MRI is the best method for radiological study, it may be normal (1). Pathogenesis of visual loss in cryptococcal meningitis is not well-known, either a direct lesion of the visual pathways and endocraneal hypertension have been described as the cause (1). In our patient SPECT-HMPAO showed bilateral occipital and left temporal lobes hypoperfusion. Although this could be due to visual deprivation, its association with other perfusion de®cits, especially in the temporal lobe, suggests a real cortical blindness, even in the absence of MRI alterations. In clinically documented cortical visual impairment, SPECT may detect focal brain dysfunction that correlates with clinical status whereas MRI can be normal or disclose only a smaller lesion. Moreover, SPECT is able to detect minor ̄uctuations in cerebral blood ̄ow such as those due to the connectivity of various regions of cerebral cortex (2). Bilateral occipital hypoperfusion observed in cortical blindness is often associated with other perfusion defects, specially in temporal or parietal lobes (2), which might re ̄ect direct central nervous system involvement due to neuronal degeneration or to impaired vascular function. Our case suggests a possible role of SPET-HMPAO for the study of Fig. 1. Tc HMPAO SPET images of the brain (oblique slices): The present case (A) is compared with the normal activity (B) and the normal MRI of the patient. The image from the present case (A) shows a slight decrease in the supratentorial cerebral blood ̄ow. Hypoperfusion of bilateral occipital and left temporal lobes is especially evident. Acta Neurol Scand 2000: 102: 340±341 Printed in UK. All rights reserved Copyright # Munksgaard 2000

Successful kidney transplantation from a brain-dead donor with ornithine transcarbamylase deficiency.

Ornithine transcarbamylase (OTC) deficiency is the most common inherited urea cycle disorder (1). Occasionally, the initial symptoms of this disease present in a late-onset form and may cause severe hyperammonemia with cerebral edema and brain death. We present a 44-year-old male patient who died of cerebral edema due to severe hyperammonemia secondary to OTC deficiency. The two kidneys were successfully transplanted in two patients. After a follow-up period of 2 years, both recipients were in stable clinical condition and graft function was good. A 44-year-old man was admitted to our hospital with progressive deterioration in his level of consciousness. He was intubated and mechanically ventilated. Initially, a brain computed tomography was normal. A lumbar puncture was performed, revealing clear and colorless cerebrospinal fluid (CSF). The biochemical study of the CSF was normal. A CSF culture for bacteria, virus, and fungi was negative. Two days after admission, the patient suffered seizures. A further brain computed tomography showed cerebral edema and plasma ammonia levels were greater than 500 Kmol/L (reference range below 50 Kmol/L). Attempts to stabilize the patient were unsuccessful, and he was declared brain dead 5 days after admission. The patient was evaluated for organ donation. The patient’s family consented to organ donation for transplantation. Renal function, ultrasonography, macroscopic examination, and perfusion of both kidneys were normal. The liver was not used for transplant due to OTC deficiency in the donor. The heart and lungs were not considered for transplantation for hypertrophic cardiomyopathy and pneumonia, respectively. An autopsy performed after organ procurement and before organ transplantation showed severe cerebral edema. The two kidneys were transplanted into two patients, aged 44 and 45 years, with a background of end-stage renal disease caused by type B abdominal aortic aneurysm dissection and interstitial nephritis, respectively. Two years after transplantation, both patients were well, and their creatinine levels were 96 and 125 Kmol/L, respectively. Neither patient has had complications to date. In the present study, our criteria to accept the kidneys for transplantation were normal renal function and structure. Investigation into the donor’s family history revealed OTC deficiency in three brothers and two daughters. Molecular analysis of the OTC gene was performed by polymerase chain reaction and a mutation (c.622G9A) in exon 6 was detected in all the donor’s family members. Evaluation and selection of all brain-dead donors (BDD) at our hospital includes routine testing for blood ammonia with simple, fast, and relatively inexpensive techniques, as in the present case. We consider plasma ammonia must be determined as part of the routine evaluation in all BDD because the OTC deficiency can be unrecognized on the day of organ donation (2). Failure to measure blood ammonia in BDD can lead to delayed or missed diagnosis of OTC deficiency, particularly when the first symptoms of this disease occur in adulthood. The isolated finding of hyperammonemia in a BDD suggests a disorder of the urea cycle. Although OTC deficiency of the donor is a contraindication for liver donation for transplantation due to the risk of lethal hyperammonemic encephalopathy for the recipient, this does not extend to organs such as kidneys, as these organs are no affected by the disease, as shown in the present report (2, 3). The enzyme activity of OTC takes place mainly in the mitochondria of the hepatocytes, and only trace levels are found in organs such as the kidneys (4, 5). The initial fatal onset of OTC deficiency can occur at age 40 to 50 years or older, as in the present case (6Y8). Diagnosis of late-onset presentations of this disorder in adults may be delayed (8). A consequence of this disorder is hyperammonemia, resulting in central nervous system dysfunction (9). Acute high levels in plasma ammonia can cause severe neurologic findings such as coma, cerebral edema, and brain death, as in the present study (7, 8). Organ transplantation from BDD with OTC deficiency has only been reported in one case in the medical literature (2). The OTC deficiency was unrecognized in the donor at the time of transplant and blood ammonia was not measured. The kidneys, lungs, and heart were successfully transplanted, but the liver recipient died of hyperammonemia and cerebral edema. The authors described the donorYrecipient transmission of this OTC deficiency via the liver transplant (2, 3). To the best of our knowledge, the present study is the second case to report successful kidney transplantation from a BDD with OTC deficiency (2). We highlight the need to consider determination of plasma ammonia as part of the routine evaluation in all BDD.

Organ donation and Rendu-Osler-Weber syndrome.

H ereditary hemorrhagic telangiectasia (HHT), or Rendu-Osler-Weber syndrome, is an autosomal dominant vascular disorder characterized by telangiectases and arteriovenous malformations in vital organs, including lungs, liver, and brain (1). Neurologic complications develop in 4% to 28% of cases and include migraine headache, stroke, seizure, intracerebral and subarachnoid hemorrhages, and brain abscess (1, 2). A brain abscess can be expected to occur in 1% of patients with HHT and the mortality rate is 40% (2, 3). To our knowledge, there are no reports describing the use of organs for transplantation from brain-dead donors (BDD) diagnosed with HHT and brain abscess. We recently evaluated a patient with HHT who meet clinical criteria for brain death secondary to a polymicrobial brain abscess. The two kidneys were transplanted in two patients. There was no donor-derived infection in the recipients. A 49-year-old female with HHT was admitted to our hospital with a pyogenic brain abscess from contiguous spread of acute sinus infection. An urgent craniotomy and drainage of the abscess was required. Microbiologic cultures of the content of the brain abscess revealed mixed flora consisting of the aerobic viridans group streptococci and anaerobic Fusobacterium and Prevotella. Viridans streptococci were susceptible to penicillin, ampicillin, cefotaxime, ceftriaxone, vancomycin, erythromycin, clindamycin, rifampin, and levofloxacin. A sample of 4 mL of purulent material was aspirated and sent for pathologic study. No evidence of brain tumor was identified. The patient received treatment with cefotaxime, metronidazole, and dexamethasone. Attempts to stabilize the patient were unsuccessful, and she was pronounced brain dead 34 hr after hospital admission. The patient’s family agreed to organ donation for transplantation. Renal function, ultrasonography, macroscopic examination, and perfusion of both kidneys were normal. Blood and urine cultures performed on the day of organ donation were negative and the results were available after organ procurement. We successfully transplanted the two kidneys in two patients. Both recipients received prophylactic antimicrobial therapy with ceftriaxone and metronidazole for 10 days after transplantation. After a short follow-up period (5 months), both recipients were in good clinical conditions and their creatinine levels were 111 and 125 Kmol/L, respectively. Neither recipient presented any complication due to the pathogens causing polymicrobial brain abscess in the donor to date. In the present study, our criteria to accept the kidneys for transplantation were normal renal function and structure and absence of metastatic infection in these organs. In the evaluation and selection of a donor with HHT and a pyogenic brain abscess, it is essential to discard genitourinary tract anomalies during organ recovery and to identify the microorganisms causing the brain abscess and their antibiotic susceptibility. Brain abscesses are often ring-enhancing, pyogenic, polymicrobial (aerobic and anaerobic mixed flora), supratentorial lesions, and without positive blood cultures, as in the present case (2, 3). It is therefore crucial to treat the donor before organ recovery and to treat the recipients immediately after transplantation with adequate bactericidal antimicrobial therapy, as in the present case. Posttransplantation follow-up of kidney recipients is the same as for donors who died from infections such as nosocomial bacterial meningitis (4). There are few reports in the literature related to genitourinary tract involvement in HHT. HHT has been associated with painless macroscopic hematuria, telangiectasia in the bladder, urethra, or prostate, and renal artery aneurysms (5, 6). In the present case, no genitourinary tract anomalies were observed during organ recovery. We reviewed the English language literature in the PubMed database using the terms ‘‘Rendu-Osler-Weber syndrome’’, ‘‘organ donation’’, and ‘‘brain abscess’’ and we were unable to identify reports of successful transplantation using organs from BDD diagnosed with RenduOsler-Weber syndrome. In summary, patients with HHT and brain death caused by polymicrobial brain abscess can be suitable organ donors. Acceptance of these donors following our protocol is safe and could increase the number of successful kidney transplants. To our knowledge, the present study is the first reported case of successful kidney transplantation from a BDD with HHTand polymicrobial brain abscess. The long-term complications and outcomes associated with organ transplantation from donors diagnosed with HHT and brain abscess require further investigation.

Esophageal ulcers in AIDS.

TO THE EDITOR: We read with interest the recent report by Wilcox and associates [1] and noted two outstanding findings: 1) the high prevalence of idiopathic esophageal ulcers and the excellent initial response to prednisone therapy and 2) the high percentage of patients with ulcer recurrence. In 13 of 35 patients with esophageal ulcers (37.1%), ulcerations recurred despite an initial clinical and endoscopic response [1]. We have recently cared for seven HIV-infected patients who had idiopathic esophageal ulcers. All had advanced disease. Three patients were initially treated with a 2-week regimen of prednisone, 0.5 mg/kg of body weight per day, but clinical and endoscopic relapse was documented between 2 and 4 weeks after the prednisone dose was tapered. Four patients initially received thalidomide, 100 mg/d for 10 days, and symptoms rapidly disappeared after treatment began. After a follow-up period of 4 to 10 months, ulceration had not recurred in our patients. In all the prednisone recipients who had ulcer recurrence, a course of thalidomide resulted in resolution of clinical symptoms and ulcer healing. No recurrence was documented in two patients during follow-up periods of 11 and 16 months, respectively. In another patient, numerous episodes of ulcerations occurred, despite effective courses of thalidomide therapy. The patient died 5 months after the first episode. Recurrence of idiopathic esophageal ulcers may represent an important problem in HIV-infected patients, both from a diagnostic and nutritional viewpoint, as Wilcox and colleagues reported [1]. Although prednisone therapy is useful for the initial treatment of HIV-associated esophageal ulcers, disease will recur in more than a third of patients [1, 2]. In our experience and in that of others [3, 4], thalidomide has been very effective in treating HIV-associated ulcerations, including idiopathic esophageal ulcerations that had not responded to prednisone therapy. Although no conclusions can be drawn from our limited number of cases, our experience is encouraging because it suggests that thalidomide can be used both as a first-choice drug or as a safe alternative to corticosteroid therapy in HIV-infected patients with idiopathic esophageal ulcerations.