New tests in neurology

We are proud in the �First Medical Lab� to launch our �Neurology Testing Center� to be the first in the middle east specialized in  testing different neurological diseases that affect our population. These tests will help the clinician in the diagnosis of different types of neuropathies, muscle diseases, dementia, blindness and deafness

Test List
Muscle biopsy and histochemical stains for all muscle enzymes
Muscle biopsy for electron microscopy
Nerve biopsy for axons and myelin stains
Nerve biopsy for electron microscopy

Acute peripheral neuropathy
Heparan Sulfate autoantibody

Chronic peripheral neuropathy
Anti-MAG, anti-Myelin-
Anti-ganglioside antibody-
GM1       GM2       GM3       GD1a     GD1b     GT1b      GQ1b
GALOP autoantibody-
(Charcot Merit (most common form  CMTA1: 80%
PMP22 duplication deletion test
:Autosomal dominant Charcot Merit evaluation-
PMP22 Dup/Del;PMP22 DNA sequencing TEST, MPZ and EGR2 DNA sequencing Test
:Multifocal Neuropathy Evaluation-
GM1 and PMP22 Duplication/Deletion Test
Myelin Protein Zero DNA Sequencing Test-
 
:Cont/ Neurology Test Lists
Sensory/Motor neuropathy profile
GALOP, anti-ganglioside GM-1, Hu, MAG, and Sulfatide antibody

Congenital blindness
Norrie Disease DNA test
Dementia

(ApoE (blood or buccal smear-
Anti-GAD-
CADASIL-

:Epilepsy
EPM1 DNA test-

Hearing loss
Connexin26 DNA sequencing Test

:Mental Retardation
Chromosome analysis-
Fragile X chromosome-
 
Motor Neuron disease
Familial Amyotrophic Lateral Sclerosis (SOD1) DNA test-
Spinal Muscular atrophy (SMA) (including (Werdig-Hoffman disease; Kugelberg-Welander  Disease )  DNA test-
 
:Movement disorders
(Ataxia profile (without Friedreich�s Ataxia  test-
SCA1. SCA2. SCA3 (MJD), SCA7, SCA8 DNA Tests
Ataxia profile with Friedreich�s Ataxia  test-
SCA1. SCA2. SCA3 (MJD), SCA7, SCA8, Friereich�s Ataxia  test DNA Tests
 Friedreich�s Ataxia  DNA test-
Multiple sclerosis IFN antibody test-

:Vertical lines of the esophageal mucosa

This entity is mostly recognized in pediatric age group and adolescents and less in adult. It is due to fibrosis of the submucosa with secondary tethered lined in the mucosa. Esophageal mucosa show infiltration by esinophils. It is considered part of allergic esophagitis

:Refractory sprue

This case although is known, the histologic features and the immunohistochemical features are more defined. In theses cases, patients have subcryptal expansion, increased myofibroblasts and increased collagen deposition in the basement membrane. A very helpful feature is markedly decreased CD 8 positive lymphocytes in the intraepithelial surface layer

:Early autoimmune gastritis AIG

Histologic changes has been defined not to miss early changes in AIG. These include lymphocytic destruction of oxyntic glands, intestinal metaplasia, parietal cells pseudohypertrophy, ECL cell hyperplasia

:(Gastropathy in pediatric age group secondary to Gastro-Esophageal Reflux (GER

This is a newly recognized association between the GER and gastritis. It is described in pediatric age group. These patients have no H.Pylori or features of autoimmune gastritis or any other causes of gastritis. When GER is treated, the gastric changes return to normal. Recognizing this entity will decrease the cost and time of investigation and leads proper management of the patients

We, in the First Medical Laboratory, are dedicated to bring the best of laboratory medicine to clinical practice to Jordan

.Dr. Hussam Abu- Farsakh, M.D

Consultant Pathologist and Cytopathologist

American boards of Anatomic, Clinical Pathology and Cytopathology

Minimal Symptomatic Celiac Sprue (low grade enteropathy): This is a sub-entity of celiac disease where the villous architecture is normal and no crypt hyperplasia. The only abnormality noted in these patient is increased lymphocytes in certain areas of the villi, with increased CD 4 expression (by immunohistochemistry). Treatment of this entity with Gluten free diet is a cure to their symptoms. Because the changes are minimal, it can pass unnoticed by the pathologist for long time

:Apoptotic colopathy

This a newly described form of colitis. These patient present with long standing diarrhea , have normal colonoscopy, usually females (but not exclusively). The pathologic changes seen is increased apoptotic foci in the crypts with increased expression of ki-67 by immunohistochemistry

Superficial Crohn’s disease

In these cases, the patient present with minimal changes of chronic inflammatory bowel disease and the lesion is limited to the mucosa. Immunohistochemistry for the Integrins is markedly increased. Treatment and follow up of these cases is as usual Crohn’s disease

We, in the First Medical Laboratory, are dedicated to bring the best of Laboratory medicine to clinical practice to Jordan

Please do not hesitate to contact us for any further details

.Dr. Hussam Abu- Farsakh, M.D

American boards of Anatomic, Clinical Pathology and Cytopathology

Introduction: A glycoprotein present in the surface membrane. This protein is important in the differential diagnosis of small blue cell tumors (large cell lymphoma, Neuroblastoma, Ewing’s sarcoma, Rhabdomyosarcoma and Primitive Neuroectodermal Tumor (PNET). Since the treatment of Ewing’s sarcoma, Extraskeletal Ewing’s sarcoma and Primitive Neuroectodermal Tumor depends very much in accurate diagnosis

:Clinical use

This test is very important in the diagnosis of Ewing’s sarcoma, Extraskeletal Ewing’s sarcoma, Primitive Neuroectodermal Tumor PNET

O13 is the only Immunohistochemical stain that is definite for Ewing’s sarcoma/ Primitive Neuroectodermal Tumor

We, in the First Medical Laboratories, are determined to bring the best of clinical practice in laboratory medicine

Please call us for any further details

.Dr. Hussam Abu-Farsakh, M.D

P16 has emerged as a valuable surrogate marker for high-risk human papillomavirus infection and shows increased immunoexpression with worsening grades of cervical intraepithelial neoplasia

The p16 gene product normally acts to inhibit progression through the cell cycle by binding to cyclin dependent kinase, thereby preventing the phosphorylation and subsequent inactivation of oncogene supressors. Several studies have shown a large percentage of low-grade squamous intraepithelial lesion (LSIL) cytology and histologic specimens to be positive for HPV types (80% to 83%). The majority of which will regress if left untreated. In all grades of CIN, and the fact that many of these lesions will ultimately regress spontaneously, other methods for detecting the potential for persistent infection and subsequent progression to higher grades of cervical neoplasia are needed. Indeed, integration of high-risk HPV sequences into the cell genome is considered to be an important event in the progression of cervical neoplasia. In addition, and likely closely

related, p16 has been shown to be a surrogate marker of infections by HPV and is proposed to be a possible prognostic marker in the progression of CIN. The direct relationship between the grade of cervical dysplasia and the intensity of p16 staining is well established. Most studies report negative p16 staining in normal or reactive cervical biopsies. Many recent studies support that p16 is a specific marker of high-grade CIN, reporting a positive predictive value of 100%. In low grade CIN (mild dysplasia), the positivity is about 30%. However, it was found that those positive low grade lesions are the one that are more likely to progress into higher grades. All studies concluded that p16 was one of the best markers for detecting CIN. In postmenopausal patients, epithelial atrophy can mimic carcinoma in Pap smears and high-grade CIN in cervical biopsies. In fact, CIN 3 may coexist with atrophy. p16. Can help to confirm CIN in this setting

Summary: p16 immunohistochemistry has emerged as a valuable diagnostic aid in the diagnosis of CIN. It has proven benefit in distinguishing high-grade cervical dysplasia from its benign mimics such as cervical atrophy, immature squamous metaplasia, reactive inflammatory lesions, and radiation induced changes. Overexpression of p16 is a useful biomarker of HPV related carcinogenesis. P16, when it is positive in low grade CIN, can predict its progression to higher CIN grade

Please contact us for any further inquiries

Dr. Hussam Abu-Farsakh

American Boards of Anatomic and Clinical pathology and Cytopathology

Virus structure and pathophysiology: autonomously replicating single stranded non-enveloped DNA which replicates when cell in S-phase. It has two components: viral capsid protein (VP) and non-structural protein (NS). VP antigen on the virus is important for interaction with host cells. The virus infects the progenitor red cells, megakaryoblast, endothelial cells and a few organs like the kidney and the heart. Non-structural protein (NS-1) exerts cell cytotoxicity while NS-2 regulates replication

Clinical manifestation: a cause of several diseases: 20% of aplastic anemia cases, a cause for non-immune hemolytic hydrops fetalis cases, fibromyalgia, renal transplant rejection like syndrome, hepatitis, myocarditis, and adult and children polyarthritis

Hydrops fetalis: it well known that Parvovirus infection during pregnancy can lead to non-immune hemolytic anemia. About 33% of the infected patietns are asymptomatic. Symptoms of infected patient can be rash, myalgia, fever, and lymphadenopathy. Best diagnostic test is IgM for parvovirus

Kidney transplant: Parvovirus can be a cause for glomerulopathy and allograft dysfunction (rejection like picture). The incidence of parvovirus infection in renal transplant patients is probably underestimated, because patients are not routinely screened for it and anemia and/or pancytopenia in these patients are often ascribed to immunosuppressive drugs. Proper diagnosis by IgM, IgG on the serum and immunostaining for Parvovirus in the biopsy material can lead to successful treatment. Eradication of Parvovirus B19 infection after renal transplantation requires reduction of immunosuppression and high-dose immunoglobulin therapy

Cancer patient: The overall prevalence of anti-B19 IgG in adult cancer patients is 60% compared to 25.0% in adult healthy patients,; it can casue or contribute to the anemia or pancytopenia patients have and usually ascribed to cytotoxic therapy

:Diagnostic tests

:The following tests are offered for Parvovirus in our lab

PCR DNA for Parvovirus in blood to detect viremia-

(Immunostaining on tissue (like in kidney transplant or in placenta of hydrops cases-

Serology tests: IgG on the peripheral blood-

We , in the First Medical Laboratory, are dedicated to bring the best of laboratory medicine in clinical practice to Jordan

Please contact for any further inquires

.Dr. Hussam Abu- Farsakh, M.D

American boards of Anatomic, Clinical Pathology and Cytopathology

Introduction: in quite afew cases, Z.N stain is positive for acid fast bacilli, while PCR for T.B is negative. The reason for this is probably that the Mycobacteria present is not of Tuberculosis species. In addition, the treatment of different Mycobacteria species requires accurate identification of the species

:Procedure and Method

Now by PCR technique, all mycobactereial species can be detected. This procedure can be performed on bronchial lavages, urines, gastric aspirate, sputum and on all body fluids. The species that are covered under this procedure are 16 types of myobacteria species and include the following

Mycobacteria tuberculosis

Mycobacteria avium

Mycobacteria celetum

Mycobacteria chelonae

Mycobacteria fortuitum 1

Mycobacteria fortuitum 2

Mycobacteria gordonae

Mycobacteria intracellula

Mycobacteria kansasii

Mycobacteria malmoense

Mycobacteria peregrinum

Mycobacteria phlei

Mycobacteria scrofulaceum

Mycobacteria xenopi

Mycobacteria Marinum

(Mycobacteria avium complex (MAC

Price: 120 J.D

We in the First Medical Lab are dedicated to bring the best of Laboratory medicine to clinical practice in Jordan

Dr. Hussam Abu-Farsakh

American Board of Anatomic & Clinical Pathology, and Cytopathology

We introduced in our �Neurology Test Center� a panel to include most cases of peripheral neuropathies due to autoantibodies. The following summary includes the most common peripheral neuropathies diseases that we examine in our lab

Anti-GM1 antibody causes conduction block, mild axonal degeneration and IgM deposits at nodes of Ranvier

IgM Anti GM1:   associated with Multifocal Motor Neuropathy (MMN) and distal motor neuron syndrome. Electrophysiology shows motor only conduction block with axonal loss. EMG shows no paraspinous denervation.. Monoclonal M-protein presents in 20% of cases

IgG anti GM1: associated with Acute Motor Axonal Neuropathy (commonly) or Chronic Distal lower motor neuron syndrome – rare

Positive tests for IgM GM1 usually indicates treatable MMN from other immune neuropathies. Best treatment is achieved by HIG, B-cell immunosuppression, plasma exchange, cyclophosphamide , with possible Rituxan

 :Anti-GM2

IgM Anti-GM2: Associated with Guillian Barre syndrome variants, Motor neuropathy and sensory demyelinating neuropathy

IgM GM2: is associated with acute neuropathy (GBS-variant), or Chronic Demyelinating Polyneuropathy

IgG GM2: associated with acute motor neuropathy with distal predominant weakness and sparing of the cranial nerves. Or chronic neuropathy with chronic axonal motor neuropathy

Anti-GQ1b: IgG-GQ1b antibodies work on binding peripheral nerves and brain stem structures and may produce presynaptic blockade of neurotransmitter release from motor nerve terminals. This disease is considered as a variant of Guillain Barrei syndrome (with ataxic features).. Monoclonal gammopathy is common in this disorder. It is associated with prodromal Campylobacter jejuni infection

Anti-GD1b: IgM-GD1b antibody cross react with antigens on red blood cells and may cause cold agglutinin.. Both IgG and IgM present in peripheral nerves on the surface of sensory neurons in the dorsal root ganglion and paranodal myelin. It is associated with sensory neuropathy +/- cranial nerve syndrome. Ataxia may develop in these patients

 
————————————————————————————–  

Cont/ Circular 49-Peripheral Neuropathy

:Anti-GD1a

IgM Anti-GD1a: associated with demyelinating motor neuropathy; and demyelinating sensory-motor neuropathy

IgG Anti-GD1a: anti GD1a associated with Guillain Barre-like syndromes, predominantly motor and axonal involvement, usually spares the cranial nerves

The disease is immune mediated with possible response with plasma exchanges or IV Immunoblobulins. Spontaneous recovery occurs in most of the people. The disease is associated with prodromal Campylobacter jejuni infection

Anti-Hu of IgG type: antibody located in neuronal nuclei. It is usually pure sensory syndrome (ganglionaopthy) with limbic encephalitis , cerebellar disorders, GI dysfunction

Anti-Yo antibodies of IgG type: antibody against Golgi apparatus in Purkinje cell cytoplasm. Associated with cerebellar syndrome in Paraneoplastic syndrome

Anti-MAG: antibodies

Anti-MAG antibodies binds to compact peripheral nervous system myelin, Schwann cell cytoplasm and occasionally axons, which causes the demyelinating process and usually it is of IgM type. The disease caused is Chronic demyelinating sensory-motor polyneuropathy, signs of sensory loss, Gait ataxia, tremor, mild distal weakness. Treated with plasma exchanges and IV cyclophosphomide and Rituxan. Associated with serum M-protein

Anti-GAD antibodies: (Glutamic Acid Decarboxylase). GAD receptors present in the cerebellum and other neurological organs associated with Stiff man syndrome (a syndrome of diffuse hypertonia of the muscles due to loss of inhibitory spinal interneurons), Amyotrophic lateral sclerosis and Cerebellar degeneration

Again, we strongly recommend to request Peripheral Neuropathy Panel for evaluation of cases with neuronal disorders

To remind you, in our lab we also do muscle biopsy (with all the muscle enzymes), nerve biopsy (with all the stains and electron microscopy), chromosomal studies, and many other neurological tests

We, in the First Medical Laboratory, are determined to bring the best of laboratory medicine in clinical practice to Jordan

Please do not hesitate to contact me for further inquiry

Dr. Hussam Abu-Farsakh

American boards of Anatomic, Clinical Pathology and Cytopathology

Circular: is a periodic circular that distributed to clinician informing them about new and important tests available at First Medical Laboratory. All information listed are supported by recent literature

:Summary

MMN                            GM1                            80

GBS                              GM1, GD1a                 20-30

Miller Fisher                  GQ1b                          95

Anti-MAG                     Anti-MAG                    50-65

Paraneoplastic              Anti-Hu

Sensory Neuropathy     Sulphatide

PlGF is a protein that is produced mainly by the trophoblasts in placental tissue. This protein is considered an angiogenic factor (it causes increase blood vessels formation), as opposed to anti-angiogenic factors (fms-like tyrosine kinase 1) that are increased also in pregnancy. The balance of both factors is the one that determines whether the patient is going to develop pre-eclampsia or not. During normal pregnancy, urinary and serum PlGF increases during the first and second trimesters, peaks at 29 to 32 weeks, and subsequently decreases. In Pre-eclampsia, the pattern shows increased PlGF in the first trimester but decreases significantly in the 2^nd trimester compared to normal pregnant patients. The presence of low PlGF in serum or urinary specimen of pregnant women carries an increased chance by 23 times, of developing pre-eclampsia before 37 weeks of gestation. In cases of pre-eclampsia, there is a drop of �Placental Growth factor� 2-3 months prior to onset of hypertension and proteinuria. This drop gives a warning signals. The patient can be advised and treated before pre-eclampsia develops Decreased urinary PlGF at mid gestation isstrongly associated with subsequent early development of pre-eclampsia

In Summary: �Placental Growth Factor� serum or urinary samples, at the mid-trimester of pregnancy, is the best predictor of pre-eclampsia. This test helps to screen women for high risk of pre-eclampsia. Special care is needed in such women to prevent progression or to keep the most dangerous complications from occurring

Dr. Hussam Abu-Farsakh

First Medical Lab Director

:References

Richard et all; Urinary Placental Growth Factor and Risk of Preeclampsia; JAMA. 2005;293:77-85

Redman C et all; Latest Advances in Understanding Preeclampsia , Science 10 June 2005; Vol. 308. no. 5728, pp. 1592 – 1594

By FISH techniques

A new service for IVF centers

The Cytogenetic Department in the First Medical Laboratory, has introduced FISH technique for PGD cases recently

:PGD is important for some cases handled in IVF centers for two main reasons

-1

Screen for common chromosomal aberrations – Down’s syndrome “Trisomy 21”; Patau syndrome “Trisomy 13” ; Edward’s syndrome “Trisomy 18”; and others

-2

Select the sex of the baby (boy or girl) to avoid diseases that are X-linked by selecting the proper baby sex

(Material required: one cell from “Planned for transfer” blastomere (6-8 cell stage) fixed on a slide (by special spreading solution

    Results are made available within few hours

The same technique is applied for cases of AMNIOCENTESIS in pregnant mothers having abnormal TRIPLE TEST and suspected of having Down’s syndrome or other chromosomal abnormalities

Please contact us before each case for proper arrangement

We, in the First Medical Laboratory, are dedicated to bring the best of laboratory medicine to medical practice to Jordan

,Dr. Hussam Abu- Farsakh, M.D.                                                        Altaf Ijmail

Am. boards Anatomic, Clinical & Cytopathology               Chief of Cytogenetic Department