DR. HASSAB EL-RASOUL SIDDIG UNITDR. HASSAB EL-RASOUL SIDDIG UNIT

Omdurman Military HospitalOmdurman Military Hospital

Presented By:Presented By:

Dr. Kamal Abdel AzeemDr. Kamal Abdel Azeem

Name :Name : عبدالرحمن حمد عبدالرحمن صفاء حمد صفاءAge :Age : 12 years 12 yearsSex :Sex : Female FemaleResidence :Residence : شنديشنديTribe :Tribe : شايقيةشايقيةD.O.A :D.O.A : 28.8.03 28.8.03

C/O:C/O:Difficulty hearingDifficulty hearingFacial weaknessFacial weaknessDifficulty swallowing Difficulty swallowing Difficulty speaking Difficulty speaking

7yrs7yrs

HPI:HPI:The pt. was an outcome of NVD at The pt. was an outcome of NVD at

home, cried after resuscitation & took the home, cried after resuscitation & took the breast. She passed through a normal breast. She passed through a normal milestones & fully vaccinated.milestones & fully vaccinated.

At the age of 5yrs, she developed At the age of 5yrs, she developed difficulty hearing and a few days later facial difficulty hearing and a few days later facial weakness. She was noticed to have inability weakness. She was noticed to have inability to raise her brows or open her eyes. to raise her brows or open her eyes.

The condition associated with difficulty The condition associated with difficulty swallowing, especially fluids.swallowing, especially fluids.

There was also difficulty speaking, her There was also difficulty speaking, her speech was low tone. No fluctuation in speech was low tone. No fluctuation in weakness was noticed.weakness was noticed.

The whole process was not preceded The whole process was not preceded by trauma, fever, sore throat, fatigability, by trauma, fever, sore throat, fatigability, nasal or ear discharge.nasal or ear discharge.No convulsion, abnormal movement, No convulsion, abnormal movement, headache or syncopal attacks.headache or syncopal attacks.No disturbance of smell.No disturbance of smell.No UL, LL or truncal weakness.No UL, LL or truncal weakness.No sphincter disturbance.No sphincter disturbance.

Systemic Review:Systemic Review:CPS:CPS:

No cough, no S.O.B, no chest pain. No cough, no S.O.B, no chest pain. No palpitation or LL swelling.No palpitation or LL swelling.

GIT:GIT: Difficulty swallowing.Difficulty swallowing. No heart burn, nausea or vomiting.No heart burn, nausea or vomiting. No abd. pain.No abd. pain. No change in bowel habits.No change in bowel habits.

Urinary :Urinary : Urine of normal amount, colour & Urine of normal amount, colour & frequency. frequency. No burning micturition or loin pain. No burning micturition or loin pain.

MSS :MSS : No joint pain, or swelling.No joint pain, or swelling. No limitation of movement.No limitation of movement. No skin changes.No skin changes.

PMH:PMH: No P.H of similar condition or admission.No P.H of similar condition or admission. Not known to be diabetic, hypertensive Not known to be diabetic, hypertensive or asthmatic.or asthmatic. No P.H of blood transfusion.No P.H of blood transfusion. No P.H of six immunizable diseases.No P.H of six immunizable diseases.

F.H:F.H: No F.H of similar condition from No F.H of similar condition from maternal or paternal side.maternal or paternal side. No F.H of DM, HT or asthma.No F.H of DM, HT or asthma.

حمد عبدالرحمن

سنة56

محمد جمالالحسن

سنة42

30yrs 28yrs 26yrs 8/12 22yrs 18yrs 12yrs

G.E

D.H:D.H: Not on long term medication.Not on long term medication. Not known to be allergic to any specific Not known to be allergic to any specific medications.medications.

S.H:S.H:The father is a Soldier & now retired.The father is a Soldier & now retired.

Primary school educated.Primary school educated. Supporting of the family.Supporting of the family. Of low S.E. status.Of low S.E. status.

O/E:O/E: Pt looked unwell, not P, J or C, a Pt looked unwell, not P, J or C, a febrile,apprehensive & not cooperativefebrile,apprehensive & not cooperative Pulse 70/min regular Pulse 70/min regular BP 110/70BP 110/70 RR 20/min regularRR 20/min regular Pt is fully conscious, orientated in Pt is fully conscious, orientated in T,P,P of average intelligence & good T,P,P of average intelligence & good memory.memory. Speech : of low tone.Speech : of low tone.

Cranial Nerves:Cranial Nerves: Normal smell & vision Normal smell & vision Normal full range eye movementNormal full range eye movement Bilateral ptosis Bilateral ptosis Bilateral LMN facial weaknessBilateral LMN facial weakness Severe weakness around the mouth, Severe weakness around the mouth, she support her chin while talking.she support her chin while talking. Sluggish palatal movement.Sluggish palatal movement. Tongue wasted & fasciculating.Tongue wasted & fasciculating. Diminished hearing.Diminished hearing. Rinnè &veber tests were impairedRinnè &veber tests were impaired

Flexion 3/5Abduction –4/5

•Normal position.

•No wasting.

•Normal tone & power.

•Reflexes all++

•Sensation intact all modalities.

•Normal position.

•No wasting.

•Normal tone& power.

•Reflexes all++

• Planter reflexes

•Sensation intact all modalities.

++++

++++

Back : normal

Gait : normal

CVSCVS

RS RS NADNAD

GIT GIT

MSSMSS

SummarySummaryThis is a 12 years old girl with This is a 12 years old girl with

bilateral ptosis,and facial and bulbar bilateral ptosis,and facial and bulbar weakness and some hearing weakness and some hearing impairment of rapidly progressive impairment of rapidly progressive course of 7 years duration.course of 7 years duration. No family history of similar condition.No family history of similar condition.

Video ClipVideo Clip

D.D:D.D:1)1) Bulbar SMA .Bulbar SMA .2)2) Myaesthenia gravis.Myaesthenia gravis.3)3) Juvenil M.N.D : (Progression of the disease. The Juvenil M.N.D : (Progression of the disease. The

appearance of pyramidal signs is invariably along appearance of pyramidal signs is invariably along the disease course).the disease course).

4)4) Congenital M. dystrophy + myopathies (CPK – EMG Congenital M. dystrophy + myopathies (CPK – EMG features).features).

5)5) Botulism (Acute reversible disease. No wasting or Botulism (Acute reversible disease. No wasting or fasciculation).fasciculation).

6)6) Diphtheria.Diphtheria.7)7) Poliomyelitis (bulbar). (the course of the disease is Poliomyelitis (bulbar). (the course of the disease is

characteristic).characteristic).8)8) Inflammatory neuropathy (sub-acute onset Inflammatory neuropathy (sub-acute onset

improvement. (EMG + NCS+CSF). improvement. (EMG + NCS+CSF).

Investigations:Investigations:

(1) CBC(1) CBCHb : 12.1G/dl TWBCs 3.4 x 10Hb : 12.1G/dl TWBCs 3.4 x 1033/cm/cmHCT : 35% Neutropil 57%HCT : 35% Neutropil 57%RBCs : 4 x 10RBCs : 4 x 1033/cm Lymphocytes 40%/cm Lymphocytes 40%MCV : 86.6FL CosinophilMCV : 86.6FL CosinophilMCH : 30.2pq Basophit 3MCH : 30.2pq Basophit 3MCHC : 34.5g/d MonocyteMCHC : 34.5g/d MonocyteESR : 32mm/1hrESR : 32mm/1hr Plt count:386 x 10Plt count:386 x 1033/cm/cm

Comment : normal morphologyComment : normal morphology

(2) UG:(2) UG: Clear Clear

(3) RFT(3) RFT Blood urea : 16mg/dlBlood urea : 16mg/dlS.creatine : 0.5mg/dlS.creatine : 0.5mg/dlS.Na+ : 140mmol/LS.Na+ : 140mmol/LS.K+ : 4.3mmol/LS.K+ : 4.3mmol/L

(4) Liver function test :(4) Liver function test :T.Bilirubin 1.1mg/dlT.Bilirubin 1.1mg/dlT.Protein 6.4g/LT.Protein 6.4g/LS.Albumin 4.3g/LS.Albumin 4.3g/LS.Globulin 2.1g/LS.Globulin 2.1g/LS.G.O.T 20U/L NR (3-18)S.G.O.T 20U/L NR (3-18)

S.G.P.T 8U/L NR (2-16)S.G.P.T 8U/L NR (2-16)

(5) S.CK : (5) S.CK : 42U/L NR (15-130)42U/L NR (15-130)

(6) Chest x-ray : (6) Chest x-ray : NormalNormal

(7) EMG(7) EMG

(8) NCS (8) NCS

* * Neostigmine test : -veNeostigmine test : -ve

These are clinically and genetically These are clinically and genetically heterogenous diseases characterized by heterogenous diseases characterized by degeneration of the AHC of the spinal cord and degeneration of the AHC of the spinal cord and bulbar motor nuclei. bulbar motor nuclei.

They lack long tract and P. nerve They lack long tract and P. nerve involvement.involvement.Synonyms:Synonyms: Bulbo-spinal m. atrophy.Bulbo-spinal m. atrophy. Hereditary motor Hereditary motor neuronopathy. neuronopathy. Progressive m. atrophy.Progressive m. atrophy.

They are classified according to:They are classified according to:

1-1- Mode of inheritance. Mode of inheritance. 2-2- Age of onset. Age of onset. 3-3- Distribution of muscle weakness. Distribution of muscle weakness. 4-4- Prognosis. Prognosis.

Classification was undergone Classification was undergone revision through the years as improved revision through the years as improved diagnostic facilities revealed more of the diagnostic facilities revealed more of the underlying molecular and genetic underlying molecular and genetic abnormalities.abnormalities.

Types:Types:

(A) Proximal limb involvement.(A) Proximal limb involvement. I) Acute infantile SMA (Werdnig Hoffman) (AR).I) Acute infantile SMA (Werdnig Hoffman) (AR). II)II) Chronic childhood SMA Chronic childhood SMA (Kugelberg Welander) (AR).(Kugelberg Welander) (AR). III) Adult onset SMA (AR).III) Adult onset SMA (AR). IV) AD juvenile SMA.IV) AD juvenile SMA. V) AD adults SMA.V) AD adults SMA.(B) Distal limb involvement(B) Distal limb involvement 7 various forms which 7 various forms which are indistinguishable from HSMN I,II (Charcot Marie are indistinguishable from HSMN I,II (Charcot Marie Tooth). Tooth). (C) Bulbo spinal(C) Bulbo spinal form (Kennedy Syndrome) x-linked. form (Kennedy Syndrome) x-linked.

(D) Occulo pharyngeal(D) Occulo pharyngeal – AD. – AD.(E) Bulbar(E) Bulbar SMA (AR). SMA (AR).

Type I :Type I : (With deafness) Vialetto-Van Laere (With deafness) Vialetto-Van Laere syndrome.syndrome.

Type II :Type II : (Without deafness) Fazio-Londe (Without deafness) Fazio-Londe disease.disease.

We believe our patient has bulbar SMA Type We believe our patient has bulbar SMA Type I, first reported by Vialetto in 1936 and later I, first reported by Vialetto in 1936 and later in 1966 by Van Laere.in 1966 by Van Laere.Onset is before age 20.Onset is before age 20.

Characterized by sensorineural Characterized by sensorineural deafness. There is facial weakness with deafness. There is facial weakness with dysarthria, dysphagia (bulbar palsy). dysarthria, dysphagia (bulbar palsy).

The progression is slow and course The progression is slow and course variable. Some patients reach adulthood.variable. Some patients reach adulthood.

There may be generalized weakness There may be generalized weakness with hypotonia and wasting. Reflexes in with hypotonia and wasting. Reflexes in limbs are present. limbs are present.

NCS + EMG demonstrate signs of AHC NCS + EMG demonstrate signs of AHC disease. disease.

Diagnosis:Diagnosis:

1)1) Characteristic history + physical exam.Characteristic history + physical exam.2)2) CPK (normal).CPK (normal).3)3) CSF (normal).CSF (normal).4)4) NCS (normal).NCS (normal).

EMG (characteristic changes of AHC EMG (characteristic changes of AHC disease. disease.

5)5) Family history. Family history.6)6) Genetic testing. Genetic testing.7)7) Muscle biopsy. Muscle biopsy.8)8) Spinal cord + brain stem histopathology Spinal cord + brain stem histopathology

(Autopsy).(Autopsy).

Management:Management:

1)1) No medical treatment.No medical treatment.2)2) Supportive management:Supportive management:* Physio – to improve mobility and prevent * Physio – to improve mobility and prevent

complication.complication.* Counseling.* Counseling.

3)3) Pts with bulbar involvement assisted Pts with bulbar involvement assisted respiration& gastrostomy. respiration& gastrostomy.

Prognosis: Prognosis: Varies with age of onset.Varies with age of onset. Early onset = early fatal outcome.Early onset = early fatal outcome.

Cause of death :Cause of death :

Pneumonia.Pneumonia. Respiratory failure.Respiratory failure. Inanition + malnutrition.Inanition + malnutrition.

Areas of Research:Areas of Research:

A)A) Genetic studies.Genetic studies.2 genes have been identify on 2 genes have been identify on

chromosome 5chromosome 5qq : the survival motor neuron : the survival motor neuron (SMN) gene, & (NAIP). the neuronal apoptosis (SMN) gene, & (NAIP). the neuronal apoptosis inhibition protein as the names imply inhibition protein as the names imply abnormalities in those genes (deletion) lead to abnormalities in those genes (deletion) lead to neuronal death.neuronal death.

B)B) Prenatal prediction & diagnosis of affected Prenatal prediction & diagnosis of affected foetuses in families with the disease. foetuses in families with the disease.