Regional Cerebral Blood Flow-SPECT in Chronic Alcoholism: Relation to Neuropsychological Testing Josep M. Nicolás, Ma M. Catafau, Ramón Estruch, Francisco J. Lomefia, Manuel Salamero, Ramón Herranz, Roser Monforte, Carlos Cardenal and Alvaro Urbano-Marquez Akohol Unit; Depamnen@r ofinteinal Medicine, Nuclear Medicine, ClinicalPsychoIo@ and Radiology; Hospital Clinic, Univei@ity ofBarcelona@ Spain of subjects (9—11).Prevalence of such alterations in Todeterminetheprevalenceofcentralnervoussystemdamage chronic alcoholics remains uncertain as does relation to dueto ethanol,we evaluated40asymptomaticchronicalcohol factors such as nutritional status and the frequency and leaand20age-matchedcontrols.Studiesincludedneuropsy amount of ethanol consumed. chologlcaltesting,brain @rc-HMPAOSPECT,and morpho We studied a homogeneous populationof asymptomatic metricanalysisbyCTscan.Inthequalitativeanalysis,30ofthe patients with chronic alcoholism, who were submitted to 40alcoholIcsshowedhypoperfusedareasonSPECTscan.In determination of rCBF using technetium-99m-hexamethyl thesemk@uanffteffveanalysis,alcoholiose@lted sign@cardre propyleneamine oxime (@Tc-HMPAO) and single photon duction in regk@nalcerebral blcod flow (rCBF) ratio of all brain emission computed tomography (SPEC!') (1Z13) under lobescomparedto controls(p < 0.001).The rCBFratiowas mainly reduced in frontal lobes (65%). Only I I alcoholics controlled conditions. Frontal and memoiy tasks were showedsignificantfrontallobeatrophyinthemorphometricanal evaluatedby neuropsychologicaltesting. Cerebralcomput ysis;mostalsohadabnormalitieson SPECTscan.Alcoholics erized tomography (CT) scan was used for atrophy correc exhibltedsignfficantimpairmentoffrontaltasksandviauospatialtion of SPEC!' perfusion deficits. sidIls.Frontaltestimpairmentwaslndependentiyrelatedto both frontalatrophyandhypoperfusion.Ina groupoftenalcoholicsIn MATERIALSAND MEIHODS whomanotherSPECTscanwasperformedafter2 moof etha Patient and Control Selection nol abstinence,rCBF ratioof the frontallobesnOrmalIZedin eight,withoutfrontalatrophy.Inpatientswithoutfrontalatrophy, Patients. Over a one-year period, 381 patients with reducedrCBFratioof the anteriorportionof the frontallobes chronic alcoholism (DSM III-R) were seen in the Alcohol correlatednegativelywithfrontaltestresults(r = —0.6535,p < ism Unit of the Hospital Clinic of Barcelona. The unit 0.001).A significantnegathiecorrelationbetweencerebralper treats only ambulatory patients who seek assistance in fusionandtheamountofethanolconsumedInthemonthpriorto terminating alcohol dependence and have no signs or sbm was observed (r = —0.6289, p < 0.001). In condusion, symptoms of other diseases. Patients with overt alcohol asyrnptomatlcchronicalcoholicsfrequentlyshowreVersiblefrOn related diseases such as liver disease, cardiomyopathy or tel lobehypoperfusion,whichis relatedto recentethanolIntake, other disorders are referredto other clinics. reflectsbrainfunctionimpairmentand Is Independentof brain On Monday of each week, the first male patient to reg atrophy. ister who had a daily ethanol consumption > 100 grams in J Nuci Msd 1993; 34:1452-1459 2 yr previous to admission, was selected for study. Ini tially, 49 chronic alcoholics were included. After percuta neous needle liver biopsy was performed on those who showed abnormalliver function tests or hepatic StrUCtUral arious studies have documented a wide range of effects abnormalities on ultrasonography, nine of the 49 were cx of chronic ethanol intake on the central nervous system cluded: five with withdrawal syndrome, two with liver (1—8).Recently,impairmentof theregionalcerebralblood cirrhosis, one who reported consumption of benzodiaz flow (rCBF) also has been observed (9—11). However, epine drugs duringthe previous 6 mo, and one with lilY. previous studies performed on human volunteers and Of the 40 patients with chronic alcoholism included in the chronic alcoholics yielded a variety of results, depending study, none exhibited causes of brain damage other than onthedoseofethanoladministeredanddifferencesintype alcoholism. No patients objected to the study and all gave informed consent for various procedures. Study protocols were approved by the InstitutionalReview Board. ReceivedDec.30,1992r@ilslonacceptedMay21,1993. For@rrespondenceandrepdr@[email protected],Depeflmento(lntemal Patients were Caucasian males of Spanish descent who Medk*@eHo@ cl1n@Vitanud170,08936Bwvelona,SpeJn. lived with their families in or around Barcelona and had 1452 TheJournalof NudearMedicine•Vol.34•No.9 •September1993 histories of stable employment. About 60% were skilled Reproduction)(21,22)aswell asvarious “frontallobe―skillssuch laborers or office workers and the rest were unskilled as the abilityto formcategories (WeiglColorSortingtest) (23,24) workers. None were indigent. and visual conceptual and visuomotor tracking (Trail Making Control Group. This group was comprised of 20 (one tests) (25). control for two patients) asymptomaticinales who did not BraInSPECT drink. They were gathered from friends and relatives of the Regionalcerebralbloodflowimageswereobtainedby SPECF alcoholics. The group was matched with the group of al using @“Tc-HMPAO(hexamethyl propylene amine oxime) coholics for age (±2 yr), sex (male) and sociocultural (Ceretec,Amersham,Intl)on the tenthday afteradmission.In the status. Members of the control group were studied in the last 10patientsofthe series, a priorSPECFwas performedon the same manner as alcoholics. dayof admission,whilemaintainingpositivealcoholemia(1.5 ± 0.78 g/liter, range 0.78—3.08),and another SPECF after two ClInIcal ExamInation months of completeethanol abstinence.Brain SPEC!' was per Using a structuredquestionnaire, one of two physicians ob formed using a rotating gamma camera (Elscint SP4-HR) tamed a detailedhistory of ethanol intakeanddietaryhabits. The equipped with a low-energy all-purpose parallel-hole collimator. data were confirmed in consultation with family members. Aver Data acquisition started 15 mm after intravenous injection of 740 age quantity per year and frequency of ethanol intake were re MBq of @“Tc-HMPAOin a silent, dimly lit room. The radio corded. Life events such as marriage,militaiyserviceand work chemical purityoflipophilic @Tc-HMPAOdeterminedby chlo posts were used as “anchorpoints―to prompt recall (“time-line! roform extraction (26) was 93.9% ±2.4%. During a 360°rotation follow-backmethod―)(14).Totalethanoldosewas estimatedby in a 64 x 64 matrixwith a zoom of 1.5, 60 x 30-sec frameswere multiplyingthe dailyamountofethanolby the numberofyears of collectedanda 4.5-mmpixelsizewas obtained.Imagedatawere each alcohol intake period times 365 and addingthe amounts of processed on an Elscint SP1 computer (Apex SP-x Functions, eachperiod.Withdrawalsymptomswereevaluatedaccordingto software version 2.0). Reconstruction was performed by ifitered the ClinicalInstitutefor WithdrawalAssessment(CIWA)scale backprojectionusinga Butterworthifiter(à utofffrequency0.35, (15,16),[email protected]).No attenuationcorrectionwasperformed.Spa None of the patientsor controlswere on medicationbeforeor tialresolutionwasapproximately16mm(FWHM)inthetransax duringtheinvestigation. ial plane. Two-pixel thick slices were obtainedin coronal, sagittal and oblique (parallel to the orbito-meatalline) planes. SPEC!' Laboratory and Nutritional StudIes images were finally presented on a polychromatic scale (20 col Withinthe firstthreedaysof admission,bloodsampleswere ors), and standardizedby adjustingthe upper discriminator obtained as baseline markers of alcohol intake and nutritional threshold to render maximumpixel values within oblique slices status. These includedhemoglobin, lymphocyte count, total pro within the most intense color table, and then applying the same tein, albumin, prealbumin, retinol-binding protein, serum aspar factor to coronal and sagittal slices. tate and alanine aminotransferases, gamma-glutamyltranspep Qualitative Analysis. The SPECF scans were coded with ran tidase, amonia, red-cell and serum folate, vitamin B12 and dom numbersand read independentlyby three nuclearmedicine erythrocyte transketolase activity, which were measured by stan physicianswho had no knowledgeof the clinicaldata. Perfusion dardsemiautomatedmethods. Serologic assays for the Venereal deficitswere consideredwhen at least two of the three observers DiseaseResearchLaboratoiy test, FluorescentTreponemalAn agreed on the evaluation of the following cerebralregions: ante tibody Absorption test, and human immunodeficiency virus anti nor (prefrontal) and posterior (superior) segments of the frontal bodies (EUSA) were also done. Hepatic ultrasonographyand lobes, anteriorand posterior segments of the temporal, parietal percutaneousneedle liver biopsywere performedin all patients and occipital lobes. withprevioushistoryof liverdisease,hepatomegalyon physical Semiquantitative An4'sis. Irregular regions of interest (ROIs) examinationand!orlaboratorydataof chronichepatocellularfail were drawnas previouslydescribedby Goldenberget al. (27). ure or abnormallyelevated serum aminotransferasesfor more Because some patients showed a diffuse supratentorial CBF fin than2 mo duringwhich the patienthad maintainedcomplete pairmentand because the most strikingfindingin the alcoholics' ethanolabstinence. SPECFimagesby visualevaluationwas the apparentabsenceof Overallnutritionwas assessed in terms of the proportionof hypoperfusion in the cerebellum, regional indices