an array of hypoperfusions

[Guest guest]

Amen's findings of hypoperfusion in many violent individuals echoes

Goldberg, Mena, etc's findings of trait-associated hypoperfusion in many

autistic kids. Perhaps Connolly et al (2) provide a glimpse towards

etiologic factors whereby the BBB becomes clogged, possibly (in some

cases) due to intra-monocyte pathogens, some of which are treatable

(3). Unclogging the BBB seems a promising avenue for many ASD kids,

especially given the example of gluten-related encephalopathy and

gluten-related frontal hypoperfusion (4).

1. from: WHY DON'T PSYCHIATRISTS LOOK AT THE BRAIN?

The Case for Greater Use of SPECT Imaging in Neuropsychiatry

By G. Amen, MD

Medical Director, The Amen Clinics

http://neuropsychiatryreviews.com/feb01/npr_feb01_spect.html

VIOLENT OR AGGRESSIVE BEHAVIOR

In my experience, SPECT is a valuable tool for evaluating patients with

violent behavior. SPECT helps to assess the functional integrity of

brain systems frequently implicated in violence, such as the prefrontal

cortex,(13-15) the temporal lobes,(14,16-18) and the anterior cingulate

gyrus.(14) Different types of deficits may require different

interventions. Thus, identifying the type of brain dysfunction a patient

has may have a major impact on clinical management.(19)

According to Raine and colleagues, emotional and unplanned acts of

violence may be the result of a person's inability to utilize his or her

prefrontal cortex to regulate the aggressive impulses that can be

generated by subcortical structures of the brain.(20) In one study,

Raine found structural deficits in the prefrontal cortex associated with

antisocial personality disorders (APD).(15) The researchers studied 21

community volunteers with APD, half of whom had committed aggressive

attacks on strangers. MRI revealed that the mean prefrontal gray matter

volume was 11% lower in the subjects with APD than in two different

control groups (34 healthy subjects and 26 matched individuals with

other psychiatric disorders).

Although this study and others have linked structural deficits in the

frontal lobes to violent behavior, a person can have a structural

evaluation that is within normal limits and yet have significant

functional abnormalities in these tissues. Thus, MRI, CT, and other

structural techniques may not provide clinical information with the same

sensitivity as SPECT and PET.

Many studies have reported blood flow and metabolic abnormalities in the

temporal lobes of violent individuals, generally in the left

hemisphere.(14,16-18) Amen and colleagues found temporal lobe

abnormalities, usually left-sided, in 72.5% of 40 adolescents and adults

who exhibited violent or aggressive behavior.(14) Soderstrom

retrospectively compared violent subjects' SPECT and MRI scans, taken

from pretrial forensic psychiatric evaluations, with those of control

subjects.(18) Even after the researchers adjusted for the presence of

major mental disorders, substance abuse, and current medication use, the

violent group displayed a significantly different functional brain

pattern. Sixteen of the 21 impulsively violent subjects showed some

hypoperfusion in the temporal and/or frontal lobes. However, MRI failed

to show any corresponding structural damage or abnormalities. A similar

study, by Volkow and Tancredi, of recidivistic violent offenders

revealed that the largest functional deficits in the temporal lobe were

found in their subjects whose structural CT scans were normal.(21)

Violent individuals have also shown atypical SPECT patterns in the

medial aspects of the frontal lobes. Amen et al found not only decreased

perfusion of the prefrontal cortex and left temporal lobe in violent

psychiatric patients, but also increased perfusion of the anterior

cingulate gyrus, a pattern associated with problems of cognitive

inflexibility and repetitive negative thoughts.(14) Work by Tiihonen et

al has also linked dysfunction of the medial frontal lobes with violent

behavior.(22)

Given the different types of brain dysfunction associated with violent

behavior, it is perhaps not surprising that the literature indicates

that specific medications may be best suited for treating particular

patterns of brain dysfunction. Several authors have suggested that

selective serotonin reuptake inhibitors are effective in treating

disorders that involve perfusion abnormalities in the medial aspects of

the frontal lobes (eg, obsessive- compulsive disorder).(23,24)

Significant rCBF reductions in the medial frontal lobes of violent

patients may help reduce these patients' tendency toward cognitive

inflexibility and repetitive negative thoughts. Anticonvulsant

medications have also been used successfully to treat violence and

aggression.(25,26)

2: J Pediatr. 1999 May;134(5):607-13.

Serum autoantibodies to brain in Landau-Kleffner variant, autism, and other

neurologic disorders.

Connolly AM, Chez MG, Pestronk A, Arnold ST, Mehta S, Deuel RK.

Departments of Neurology and Pediatrics, Washington University, St. Louis

Children's Hospital, St Louis, Missouri, USA.

OBJECTIVE: Etiologically unexplained disorders of language and social

development have often been reported to improve in patients treated with

immune-modulating regimens. Here we determined the frequency of autoantibodies

to brain among such children. DESIGN: We collected sera from a cohort of

children with (1) pure Landau-Kleffner syndrome (n = 2), (2) Landau-Kleffner

syndrome variant (LKSV, n = 11), and (3) autistic spectrum disorder (ASD, n =

11). None had received immune-modulating treatment before the serum sample was

obtained. Control sera (n = 71) were from 29 healthy children, 22 with

non-neurologic illnesses (NNIs), and 20 children with other neurologic disorders

(ONDs). We identified brain autoantibodies by immunostaining of human temporal

cortex and antinuclear autoantibodies using commercially available kits.

RESULTS: IgG anti-brain autoantibodies were present in 45% of sera from children

with LKSV, 27% with ASD, and 10% with ONDs compared with 2% from healthy

children and control children with NNIs. IgM autoantibodies were present in 36%

of sera from children with ASD, 9% with LKSV, and 15% with ONDs compared with 0%

of control sera. Labeling studies identified one antigenic target to be

endothelial cells. Antinuclear antibodies with titers >/=1:80 were more common

in children with ASD and control children with ONDs. CONCLUSION: Children with

LKSV and ASD have a greater frequency of serum antibodies to brain endothelial

cells and to nuclei than children with NNIs or healthy children. The presence of

these antibodies raises the possibility that autoimmunity plays a role in the

pathogenesis of language and social developmental abnormalities in a subset of

children with these disorders.

PMID: 10228297 [PubMed - indexed for MEDLINE]

3: Med Hypotheses. 2001 Apr;56(4):523-31.

Intra-monocyte pathogens delineate autism subgroups.

Binstock T.

Immune panels of many autism-spectrum children reveal signs of atypical

infections and shifted cell counts. In conjunction with trait-related cerebral

hypometabolism and hypoperfusion, these findings suggest a hypothesis: Several

autism-spectrum subgroups derive from intra-monocyte pathogens such as measles

virus, cytomegalovirus, human herpesvirus 6, and Yersinia enterocolitica.

Furthermore, with much inter-child variation, their effects manifest as

diminished hematopoiesis, impaired peripheral immunity, and altered blood-brain

barrier function often accompanied by demyelination. In some such children, one

or more of these pathogens persists as a chronic-active, seemingly subclinical

infection etiologically significant to the child's autistic traits. Within these

subgroups, immune impairments and atypical infections may be treatable.

Copyright 2001 Harcourt Publishers Ltd.

PMID: 11339860 [PubMed - indexed for MEDLINE]

4. Dig Liver Dis. 2004 Aug;36(8):513-8.

Frontal cortical perfusion abnormalities related to gluten intake and

associated autoimmune disease in adult coeliac disease:

99mTc-ECD brain SPECT study.

Usai P, Serra A, Marini B, tti S, Satta L, Boi MF, Spanu A, Loi G,

Piga M.

Department of Nuclear Medicine, University of Cagliari, Cagliari, Italy.

usaip@...

OBJECTIVE: Since brain perfusion abnormalities have been described by

single-photon emission computed tomography in some autoimmune diseases, the

aim of the present study was to evaluate the incidence of perfusion

abnormalities by brain single-photon emission computed tomography in a

group of coeliac disease patients, and to investigate whether gluten intake

and associated autoimmune diseases may be considered risk factors in

causing cerebral impairment. METHODS: Thirty-four adult coeliac patients

(16 on a gluten-free diet and 18 on a gluten-containing diet, 18 (53%) with

autoimmune diseases) underwent 99mTc-ethyl cysteinate dimer brain single-

photon emission computed tomography and qualitative evaluation of brain

perfusion was performed together with a semiquantitative estimation using

the asymmetry index. Ten subjects on our database, matched for sex, age and

ethnic group, who were proved normal by histology of jejunal mucosa (four

males and six females; median age 39 years, range 27-55 years), were

included as control group. RESULTS: Twenty-four out of 34 patients (71%)

showed brain single-photon emission computed tomography abnormalities

confirmed by abnormal regional asymmetry index (>5%; range 5.8-18.5%).

Topographic comparison of the brain areas showed that the more significant

abnormalities were localised in frontal regions, and were significantly

different from controls only in coeliac disease patients on unrestricted

diet. The prevalence of single-photon emission computed tomography

abnormalities was similar in coeliac disease patients with (74%) and

without (69%) associated autoimmune disease. CONCLUSIONS: Abnormalities of

brain perfusion seem common in coeliac disease. This phenomenon is similar

to that previously described in other autoimmune diseases, but does not

appear to be related to associated autoimmunity and, at least in the

frontal region, may be improved by a gluten-free diet.

PMID: 15334770 [PubMed - in process]