Sunday, May 24, 2020

CASE SCENARIO : PARA-PARESIS III

CASE 3
COMPLETE CASE REF -

18 y/o M with CC of  difficulty in walking since 1 month,  was insidious on onset and gradually progressing reaching a point where he finds difficulty in climbing stairs, in holding chappals, standing after sitting ; he complains of PAIN in calf muscles with positive CALF TENDERNESS; there is h/o FEVER and WASTING of muscles ; h/o slipping off of chappals w/o knowledge ; h/o alcohol consumption twice every week.

 NEGATIVE HISTORY - NO H/O SIMILAR DIFFICULTY IN UPPER LIMBS OR CRANIAL NERVE INVOLVEMENT ; NO H/O AUTONOMIC NERVOUS SYSTEM ISSUES  

 ANALYSIS : PATHOLOGY COULD BE - 

  • VASCULAR
  • MUSCULOSKELETAL
  • IN CNS
  • IN PNS
POSITIVE FINDINGS ON CLINICAL EVALUATION

  • Moderate built and poor nourishment 
  • Pallor - present
  • Bulk of the muscles in B/L UL and LL is decreased - suggesting wasting
  • Hypotonia in B/L LL with normal UL
  • Decreased Power in B/L LL with normal UL 
  • Plantar Reflex is MUTE 
  • Deep Tendon Reflexes are absent B/L in both UL and LL
  • Positive Calf Tenderness
ANALYSIS BASED ON HISTORY AND CLINICAL FINDINGS :

18 y/o anemic pt with muscle pain, weakness, wasting. With mute plantar reflex and absent deep tendon reflexes in both B/L UL and LL with h/o slipping off of footwear w/o knowledge and  h/o fever.

 It is an LMN Lesion which could be inflammatory along with peripheral neuropathy.

 Points to be kept in mind for arriving at a differential diagnosis - 

  • Age of onset
  • Acute onset, pain, weakness with h/o fever 
  • Weakness is symmetrical and gradually progressing in LL 
  • Mental functions are intact
  • No h/o intermittent claudication pain / edema in LL with skin changes, ruling out vascular pathology
  • No h/o Diurnal Variation/relief on exertion of the weakness ruling out major NMJ disorders
  • Pain could be due to compression of nerves/ pathology in muscle 

DIFFERENTIAL DIAGNOSIS WITH SPECIFIC INVESTIGATIONS :

  • Polyneuropathy 

Etilogy is varied. Investigations required are as follows -

 - GRBS, THYROID PROFILE, LFT, RFT to rule out endocrine, liver/ renal causes
- PERIPHERAL SMEAR to look for evidence of subacute combined degeneration of Spinal Cord
- Vitamins B12, B1, B6 , E deficiency ; Pyridoxine excess
- Alcohol induced
- Ruling out infectious causes ; ESR
- INFLAMMATORY CAUSES LIKE 

  1. Gullian Barre - LUMBAR PUNCTURE, ELECTROMYOGRAPHY [EMG] , NERVE CONDUCTION STUDY [NCD]
  2. Chronic Inflammatory Demyelinating Poyneuropathy - EMG, NSD, Sural Nerve Biopsy, USG of Peripheral Nerves
  3. VASCULITIS DUE TO SLE/Sjogren's/Rheumatoid Arthritis/ Polyarteritis Nodosa - ESR, Anti-Nuclear Antibodies, Rheumatoid Factor, anti-CCP Antibodies
- Amyloidosis - tissue biopsy
- Could be Paraneoplastic
- Hereditary causes - Charc0t-Marie-Tooth-Disease/Familial Amyloidosis - NCS, Nerve Biopsy, Genetic Testing

  • Radiculopathy due to intervertebral disc herniation in Lumbar region 
- B/L SCIATICA CAN BE CAUSED TO DUE SPINAL STENOSIS
-Spinal stenosis can be caused due to varied etiology 
-INVESTIGATIONS : 1. MRI and X-ray   2. CT myelogram 
- Physical test for confirmation of sciatica is Straight leg raise to produce Lazarević's sign. 

  • Myopathies
- Becker's muscular dystrophy
- Limb Girdle muscular dystrophy
- Myopathies due to enzyme deficiencies
-Infections causing myopathies
- Systemic conditions like Sarcoidosis, etc

 Most Myopathies can be detected by-

 EMG, NCS, CREAITINE KINASE LEVELS IN SERUM, MUSCLE BIOPSY AND GENETIC TESTING

 INVESTIGATIONS DONE ON THE PATIENT

  • Serology - All negative
  • Chest X -ray - Normal
  • Creatinine Kinase Levels - Normal
  • T3 - Decreased
  • NCS - Shows B/L common peroneal and sural axonal neuropathy.
  • Sural Nerve Biopsy was planned
  • Later pt was found to have Scabies also.
ANALYSIS- 

 -Normal creatinine levels rule out anyform of active myopathy.

[Though Hypohyroid Myopathy can occur in some cases, but CK levels would be elevated in such cases]
- Common Peroneal Neuropathy is seen in Pts who are thin built/ sit cross-legged quite often/ wear tight-fitting foot-wear/Charcot-Marie-Tooth Disease/Polyarteristis Nodosa

DIAGNOSIS GIVEN TO THE PATIENT

 Paraparesis secondary with B/L Common Peroneal and Sural Neuropathy with Scabies.

 TREATMENT

  • Tab PARACETAMOL 650 mg TID 
  • Injection NEOMOL 100ml i.v. infusion if Temp increases >101 F
  • PERMETHRIN 5% LOTION overnight, to be applied on entire body except face
  • Tab B COMPLEX OD
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Saturday, May 23, 2020

CASE SCENARIO : PARA-PARESIS II

CASE 2

18 y/o M presented with CC of -
B/L LL WEAKNESS SINCE 20 DAYS ; Started 2 y/o insidious on onset and gradually progressing, starting from proximal to distal region of both LLs.
H/o B/L Non pitting edema in LLs. 
He complains of difficulty in squatting and resuming upright position post-squatting, Difficulty in wearing and holding chappals.

NEGATIVE HISTORY - NO PROBLEM IN USING UPPER LIMBS AND NO HISTORY INDICATING CRANIAL NERVE INVOLVEMENT.

Priority Problems - 

  • B/L LL Weakness leading to inability to perform daily chores.
  • B/L LL Non pitting edema.
ANALYSIS - Pathology in

  • VASCULAR - ARTERIAL/VENOUS
  • CNS
  • PNS
  • MUSCULOSKELETAL SYSTEM
POSITIVE FINDINGS ON CLINICAL EXAMINATION 

 [For Complete examination pls refer the original case, link provided in the beginning]

  • Power in both LL in 4/5
  • Areflexia 
  • Normal Sensory system with no meningeal/cerebellar signs
  • GRBS - 142mg/dl
ANALYSIS AND DIFFERENTIAL DIAGNOSIS BASED ON KNOWN HISTORY AND CLINICAL FINDINGS

  • ARTERIAL Cause is ruled out - no complaint of claudication pain.

  • VENOUS cause - B/L Non pitting edema, Chronic Venous Insufficiency ?

  • LYMPHATIC OBSTRUCTION - May lead to non pitting edema. Filariasis /Severe Infection/ Chronic Inflammatory Condition?

  • CNS - Areflexia with muscle weakness rules out possibility of UMN Lesion. It is an LMN Lesion.

  • PNS - Lumbo-Sacral plexus provides the nervous supply to LL and its compression presents with pain and other symptoms; BUT THERE IS EVIDENCE OF PERIPHERAL NEUROPATHY

  • NEURO-MUSCULAR JUNCTION - Weakness could be Because of pathology in NMJ. Myasthenia Gravis and Lambert Eaton Myasthenic Syndrome fit the Pt profile to more extent than other NMJ disorders , this does NOT mean to say that the focus of damage is NMJ.
- Myasthenia Gravis : Sometimes patients with MG present with Limb muscle weakness only, even though most common symptoms are ocular and facial. There are atypical presentations as described in  -
https://pubmed.ncbi.nlm.nih.gov/27854225/?from_term=Myasthenia+gravis+limb+weakness&from_pos=5

''Patients with atypical/unusual MG onset were the 4.4% of all MG patients population. We describe seven different clinical categories: asymmetric distal upper limbs weakness, foot drop, isolated triceps brachii weakness and foot drop, post exertional axial weakness with dropped head, acute facial dyplegia, limb-girdle MG and MG with sudden lower limbs weakness and recurrent falls.''

 But there is NO H/O FLUCTUATING WEAKNESS and ONLY LOWER LIMBS SEEM EFFECTED WHICH COUNTERS THE CLAIM w.r.t Myasthenia Gravis in this particular case.

 - Lambert-Eaton-Myasthenic Syndrome : Effects proximal muscles of the limb and Lower limbs are more effected than upper limbs. BUT THE WEAKNESS IS RELIEVED AFTER ANY FORM OF EXERTION. 
From the history, one can infer that weakness was gradually progressive, hence LEMS is ruled out.

 NMJ DISORDERS SEEM UNLIKELY, GIVEN THE PT HISTORY AND CLINICAL FINDINGS. 
  • MUSCLE DISEASE : With defect in muscle itself, referred to as MYOPATHY .
Myopathies could be PRIMARY AND SECONDARY in nature. NOW, POINTS TO BE KEPT IN MIND WHILE ARRIVING AT THE DIFFERENTIAL DIAGNOSIS IS 

  1. Slowly progressive, painless, symmetrical proximal lower limb weakness followed by distal limb weakness
  2. Upper Limb Functions and other motor functions like speech, swallowing are intact
  3. Mental functions intact
  4. Age of onset - adolescence to early adulthood
Based on the above, DDs are - 

  1. Becker's Muscular Dystrophy
  2. Limb-Girdle Muscular Dystrophy
  3. Sporadic late onset nemaline myopathy
  4. Endocrine Myopathy
  5. Polymyositis
DIFFERENTIAL DIAGNOSIS WITH SPECIFIC INVESTIGATION
  • MYASTHENIA GRAVIS Class IIa
- Edrophonium Chloride Test
- Ice Pack Test
- Electrophysiological Tests :  REPETITIVE NERVE STIMULATION / SINGLE FIBRE ELECTROMYOGRAPHY

  • BECKER'S MUSCULAR DYSTROPHY 
- Serum Creatinine Kinase [CK] Levels
- Electromyography [EMG]
- Muscle Biopsy
- Genetic testing

  • POLYMYOSITIS 
- Serum Creatinine Kinase and Aldolase Levels
- Electromyography
- Electromyography

  • LIMB GIRDLE MUSCULAR DYSTROPHY 
- ECG
- EMG
- Serum CK Levels
- MRI

  • SPORADIC LATE ONSET NEMALINE MYOPATHY 
- EMG
- MRI
- Needle Biopsy

  • ENDOCRINE MYOPATHIES 
- Serum TSH, T3, T4
- Serum Cortisol
- Serum PTH
- Serum Calcium

INVESTIGATIONS AND DIAGNOSIS DONE FOR THE PATIENT

 Consists of abnormal findings, for complete investigations, pls refer to the link of the original reference.

  • ELEVATED GRBS - 142mg/dl - PRE DIABETIC
  • PERIPHERAL SMEAR - NORMOCYTIC NORMOCROMIC WITH LEUKOCYTOSIS
  • ELEVATED TLC WITH LYMPHCYTOSIS 
  • ELEVATED UREA, URIC ACID, CREATININE, PHOSPHORUS, CHLORIDE IN RFT
  • ALBUMIN PRESENT IN URINE
  • MUSCLE BIOPSY GIVES EVIDENCE OF ATROPHY/NECROSIS OF MUSCLE FIBRES ; IMPRESSION OF POLYMYOSITIS/MUSCULAR DYSTROPHY
DIAGNOSIS - MUSCULAR DYSTROPHY 

QUESTIONS -


  • PT HAS ELEVATED LEVELS OF COMPONENTS IN RFT, OUT OF WHICH FEW ELEVATIONS CAN BE EXPLAINED w.r.t THE CORTICOSTEROID THERAPY AND SALICYLATE THERAPY, OTHERS ARE NOT. ALBUMIN IS SEEN IN URINE, COULD THE PT HAVE CHRONIC RENAL PATHOLOGY ?
  • CHANGE IN MUSCLE WEAKNESS w.r.t TEMPERATURE ?
  • HOW LONG HAS THE NON PITTING B/L LL EDEMA BEEN THERE ? DID IT CHANGE TO NON-PITTING TYPE OVER A PERIOD OF TIME?
  • 2 YEARS IS A LONG TIME, DID THE PATIENT NOT SEE ANY OTHER PHYSICIAN ? RELEVANT DRUG HISTORY WHICH MIGHT HELP ?
  • COULD HE BE PRONE TO DIABETES ?
  • COULD THE REASON FOR B/L NON PITTING LL EDEMA BE MUSCULAR WEAKNESS WHICH LEADS TO DECREASED VENOUS RETURN AND VENOUS STASIS, OVER A PERIOD OF TIME CAUSING FIBROSIS ?
ANSWERS TO QUESTIONS POSED BY FACULTY 

  • ANATOMICAL LOCATION OF LESION 
-  SKELETAL MUSCLE 

  • MOST LIKELY ETIOLOGY AND PATHOLOGY 
- MUSCULAR DYSTROPHIES ARE 
     '' non-inflammatory degenerative conditions of muscle that are genetically determined, not effectively curable, and progressive. The types of muscular dystrophy are usually classified according to inheritance and distribution of weakness ''
https://www.dartmouth.edu/~dons/part_3/chapter_21.html#chpt_21_muscle

- Most common mutation is in the gene coding the PROTEIN DYSTROPHIN which is important for muscle contractions to occur. Age of presentation and severity depends on the severity of mutation in coding dystrophin and pattern of inheritance.
  • THERAPEUTIC OPTIONS 
- NON PHARMACOLOGICAL 
1. AVOIDANCE OF INACTIVITY FOR A LONG DURATION
2. PHYSIO-THERAPY
3. ORTHOPEDIC APPLIANCES TO HELP IN MOTILITY, STABILITY AND SELF CARE.
-PHARMACOLOGICAL
- PREDNISONE HELPS IN PRODUCTION OF THE PROTIEN UTROPHIN WHICH RESEMBLES DYSTROPHIN AND SLOWS MUSCULAR DETERIORATION IMPROVING THE QUALITY OF LIFE.

The above is supported by a RCT linked below -


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Friday, May 22, 2020

CASE SCENARIO 2 - PARA-PARESIS I

CASE 1


23 y/o male auto-driver came with a complaint of B/L Lower Limb Weakness since 5 DAYS ; ALSO A SUDDEN FALL WHEN HE ASCENDED TO URINATE along with Tingling and numbness in the lower extremities . He gives history of Vomiting non-projectile and non bilious.
5 months ago, was diagnosed with a PSOAS ABSCESS which was drained. 10 days back, A scrotal abscess was drained.
He has had a history of multiple sexual partners. 

Priority Complaint - 
  • Weakness in B/L LL since 5 days ; difficulty to carry out life tasks.
Analysis - Acute onset Lower Limb weakness - Causes could be problem in
  • CNS
  • PNS
  • Musculoskeletal system 
POSITIVE FINDINGS ON CLINICAL EXAMINATION - 
  • Hypotonia of Both Lower Limbs
  • Power of Rt and Lt LL is 2/5 and 0/5 resp.
  • Plantar reflex is Extensor
  • Right Sided Deep Tendon reflexes are more reactive with Rt Knee and Ankle Jerk scoring 3+ and Ankle Clonus present on Rt side.
Analysis - 
  • Hypotonia could mean [A] LMN Lesion [B] Initial Stages of UMN Lesion
  • Decreased LL power score according to MRC SCALE of                                                                    2/5 on Rt meaning - active movement present when gravity is eliminated                           0/5 on Lt meaning - No contraction
  • Extensor Plantar reflex - Babinski's sign positive - UMN lesion 
  • 3+ score in deep tendon reflex elicitation indicates VERY BRISK RESPONSE, MAY/MAY NOT BE NORMAL AND POSITIVE ANKLE CLONUS in Rt LL with normal response of 2+ in Lt LL indicating a probability of UMN Lesion
CAUSES -
  • In case of UMN lesion - BRAIN, SPINAL CORD
  • In case of LMN lesion - SPINAL CORD , PERIPHERAL NERVES , NEUROMUSCULAR JUNCTION, MUSCLE 
         - Tingling and numbness maybe Peripheral Neuropathy
         -  Autoimmune NMJ disoders, seen in HIV patients due to immunodeficiency.
            [LEMS - Lambert Eaton Myasthenic Syndrome]
         - Muscular Pathology 
  • Vascular - Ruled out as there is no h/o Intermittent Claudication Pain/Edema of LL with Skin Changes. 
  • Trauma - No h/o Trauma
  • Anemia - No pallor, ruled out.
ATTEMPT TO LOCALIZE WITH KNOWN HISTORY AND CLINICAL FINDINGS - 
  • 23 M, acute onset B/L LL weakness, h/o multiple sexual partners, past h/o psoas abscess shows B/L LL hypotonia, muscar weakness, + Babinski's sign, probable hyper-reflexia and ankle clonus on Rt side. Upper Limbs are normal.
  • The above signifies findings in support Initial stages UMN Lesion and some LMN Lesion signs in lower limb with Normal upper limbs
  • HENCE, THE LESION COULD BE BETWEEN T3 - L3 or BETWEEN L4 - S2.
FEW DIFFERENTIAL DIAGNOSIS -
  • POTT'S DISEASE / TUBERCULOSIS SPONDYLITIS - 
- Mode of infection is mostly, Hematogenous spread of Mycobacterium tuberculosis from an extraspinal site like lungs.
- Infection reaching adjacent ligaments and soft tissues may be lead to formation of COLD ABSCESS. SPREAD OF INFECTION FROM LUMBAR VERTEBRAE TO PSOAS MUSCLE, FORMING A COLD ABSCESS. Patient has a history of psoas abscess 5 months ago.
- Neurological symptoms in Pott's diesease can occur at anytime and present with PARESIS, ABNORMAL TONE AND REFLEXES.
- In some cases bacteria invades the Dura and can lead to Meningitis/Tuberculoma causing symptoms such as vomiting.
- Since he exhibits high risk behavior, he has to repeatedly be tested for HIV. HIV cannot be detected during window period [6-12 weeks after exposure]. TB is one of the most common Co-Morbidities of HIV.
INVESTIGATIONS - 
1. Complete Blood Picture, ESR and RBS 
2. Liver Function Test
3. Kidney Function Test
4. Serology - HIV, HbsAg, Anti HCV antibodies, VDRL 
5. Culture to isolate the organism causing Psoas Abscess
6. CSF Analysis
7. Mantoux Test
8. NAAT for Rapid Sputum Examination
9. Chest X-ray
10. MRI - Brain and Spinal Cord

TREATMENT - 

1. Treatment Goals - [a] To confirm diagnosis and eradicate the infection
                                  [b] Recover/maintain neurological function
                                  [c] Functional return to everyday tasks
2. Treatment Proper - [a] Anti TB Therapy 
                                   [b] Surgical Spinal Cord Decompression/ Surgical Spinal Fusion/ Spinal                                                     Immobilization, if indicated.
                                   [c] Analgesics
                                   [d] Physio Therapy
3. Indicators of Good Prognosis -  [a] Young Age
                                                       [b] Good General Conditions
                                                       [c] Short duration of neural complications
                                                       [d] Early onset cord involvement with late onset neural symptoms
  • MULTIPLE SCLEROSIS - 
- Occurs in 20s, Initial symptom can be weakness in lower extremity with tingling and numbness.
- It is a demyelinating disease with varied etiology.

SPECIFIC INVESTIGATIONS -

1. CSF Analysis
2. MRI Brain and Spine
3. Evoked Potential Test 
4. Blood Tests for ruling out conditions similar to MS 

TREATMENT - 

A. NON PHARMACOLOGICAL - 
     1. Physio Therapy
     2. Dietary Modifications -  Preliminary research regarding dietary interventions helping in                                                               controlling chronic inflammatory disorders. Links of which are below,


             [a] Probiotics in diet improve health and reduce disability
             [b] Vitamin D supplementation 
             [c] Fish Oil Supplementation
             [d] Ketogenic Diet 

B. PHARMACOLOGICAL - 
     1. Acute Relapse Management - a. Prednisone                                                                                                                                          b. Plasmapheresis

     2. Disease Modifying Agents -   a. Beta Interferons                                                                                                                                  b. Natalizumab                                                                                                                                        c. Fingolimod
                                                      d. Glatiramer acetate
                                                     e. Mitoxantrone
  • SPONDYLODISCITIS - 
- Rare but serious disorder in which there is a primary infection of the inter-vertebral disc with secondary infections of the vertebrae, starting at the end plates. Mostly associated with E.coli / M.tuberculosis. In this case, there is a strong evidence of TB.

INVESTIGATIONS SAME AS FOR POTT'S DISEASE EXCEPT HERE, GADOLINIUM ENHANCED MRI IS PREFERRED.

TREATMENT - 

A. NON-PHARMACOLOGICAL - Physio Therapy 

B. PHARMACOLOGICAL - 

a. CONSERVATIVE TREATMENT - 
Carried out for 4 - 6 weeks. Indicated only in mild cases/when surgery is too risky. Anti-Tubercular Therapy ; Immobilization of Spine esp. in cases of ventral column/ Lower Lumbar or Lumbo-sacral Involvement for maximum for six weeks after which there are high chances of pseudoarthroses and kyphotic malposition of spine. 
In Children immobilization is not done.
b. SURGERY - 
ATT with radical surgical debridement and stable reconstruction.

  • INTRA CRANIAL TUMOUR

  • STROKE - B/L Anterior Cerebral Artery Infarction [rare]

INVESTIGATIONS DONE FOR THIS CASE - 

For complete detail, pls refer to the link of the case.  

ABNORMAL FINDINGS ARE 

  • ESR ELEVATED - PROBABLY DUE TO INFLAMMATION
  • SGOT, SGPT ELEVATED - It could be due to ATT, but was the LFT done after starting patient on drugs ? Other causes could be Myopathy.
  • ALKALINE PHOSPHATASE ELEVATED 
  • CREATININE SLIGHTLY REDUCED - Lower muscle mass? Diet low in protein ? 
  • LYMPHOCYTE COUNT REDUCED - Chronic infection ? Was ATT started before the blood examination ?
  • CHEST X-RAY - Coarse reticulonodular densities distributed throughout the parenchyma on both sides, probably Miliary tuberculosis.

X-RAY ABDOMEN - Shows left psoas abscess



  • MRI BRAIN - 
           Meningeal enhancement/ exudates with multiple nodules in pulmonary apices suggesting             pulmonary koch's and disseminated TB. Ring enhancing lesion in Rt and Lt Cerebral                 Hemispheres.









             





































DIAGNOSIS GIVEN - L4, L5 Infective spondylodiscitis with paraparesis, left psoas abscess and ring enhancing lesions in RT and LT  Cerebral Hemishperes.

TREATMENT - 
1. ANTI TB THERAPY 
2. T.Benadon 40mg/ OD
3. T.Pregabalin 75mg/po/h/s
4. OINT. MEGAHEAL AND SITZ BATH WITH BETADINE TID
5. FREQUENT CHANGE OF POSITION

Questions - 

1.WHAT IS THE REASON FOR 
  • Elevated Liver enzymes and reduced Creatinine and Lymphocytes
  • Frequent Change of Position recommended to the patient
  • Rt sided reflexes being more pronounced than left sided ? Does is have anything to do with Lt sided enhancement being more than Rt side in the MRI as pyramidal tracts cross-over at lower medulla ?
2. WHEN HE FELL, DID HE JUST FALL BECAUSE HIS LEGS WERE WEAK / HE LOST HIS BALANCE / HE BECAME UNCONSCIOUS ?

SUGGESTION -

  • Electromyography to rule out muscle problems in case of no reason to justify elevated liver enzymes.
  • Repetation of HIV testing for 12 weeks - 6 months to rule out false negative status due to widow period.


SOURCES

 ANSWERS TO THE QUESTIONS POSED BY THE FACULTY - 
1. ANATOMICAL STRUCTURES CAUSING PARA-PARESIS 
Ans - Insult in Brain, Spinal cord at the level of L4, L5 verterbrae

2. MOST LIKELY ETIOLOGY AND PATHOLOGY IN THE ANATOMICAL LOCATION
Ans-  Spread of TB from lungs to vertebrae mostly via blood. Once spread, it may infect vertebrae, inter-vertebral discs, epidural or intra-dural space within the spinal canal or adjacent tissues. Infection may go upwards or downwards, destroying the anterior and posterior longitudnal ligaments and periosteum from the front and sides of the vertebral bodies. Cold abscess [PSOAS ABSCESS] can form if the infection reaches the adjacent ligaments and soft tissues.
Neurological symptoms can occur at any point of time.
In this case, L4, L5 are infected and probably the inter-vertebral disc between both of them leading to para-paresis of both lower limbs. Infection ascended to brain also, as seen in MRI

3. THERAPEUTIC OPTIONS 
Ans- As mentioned above near Pott's Disease and Spondylodiscitis. 
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Thursday, May 14, 2020

GENERAL MEDICINE CASE DISCUSSION

[14 MAY 2020]
ROLL NO - 38


The case given was of  - 42 y/o female diagnosed with GLUCOSE 6 PHOSPHATE DEHYDROGENASE AND ADENOSINE MONOPHOSPHATE DEAMINASE DEFICIENCIES WITH VARIOUS OTHER PROBLEMS.

 Case reference - https://classworkdecjan.blogspot.com/2019/05/42-f-with-severe-regular-edema-with_17.html?m=1

My basis of Prioritizing -

Pt wants to continue hiking and pursue her ambitions without increased / severe somatic and mental symptoms and according to me, most problematic symptoms are

  • Frequent fluctuation of weight
  • Shortness of Breathe
  • Weakness, Numbness, Non-functioning of her limbs 
  • Severe Blinding and vertigo inducing headaches
  • Decreased/Absent REM sleep
MY EXPLANATION TO HER SYMPTOMS AFTER ACQUIRING THE DIAGNOSIS IS AS FOLLOWS 

[A] G6PD DEFICIENCY 

G6PD is the most important enzyme in HMP Shunt Pathway as it is responsible for the        formation of NADPH and is a part of oxidative and irreversible part of the reaction. 
Moreover being the first step of the reaction.

HMP SHUNT is ONE OF THE major sources of NADPH. And has the following funtions - 
  1. Reductive biosynthesis of cholesterol, steriods, fatty acids
  2. Free radical scavenging in RBCs, Lens, and keeping Fe in ferrous state in Hb.


SYMPTOMATOLOGY AND DIAGNOSIS PERTAINING TO G6PD
  • Hemolysis - Severe jaundice at birth, edema in face/neck/trunk, Severe reaction to sulfa drugs and anti-malarial agents, Favism ; Pallor, Icterus [some cases], Edema, Hepato-splenomegaly [cannot be seen in case of increased edema]
  • Investigations- [That are generally done, not this case in particular]
  1. Complete Blood Count - Heinz Bodies seen in active disease
  2. Reticulocyte count
  3. Serum LDH - Elevated in case of Hemolysis 
  4. Total, Direct and Indirect Hemoglobin 
  5. Coombs Test - negative as G6PD is not immune mediated 
  6. Beutler Flourescent Spot Test - Rapid test for visual identification of NADPH produced by G6PD under UV Light. [false negative in active hemolysis; also done in GALACTOSEMIA]
TREATMENT
  • Avoidance of Foods, Drugs precipitating hemolysis 
  • Folic Acid Supplemtation to increase RBC turnover 
  • Blood Tranfusion/Dialysis if indicated
  • Protection from infections as they may precipitate Hemolysis - Vaccination
[B] AMPD1 DEFICIENCY

AMP Deaminase is responsible for converting AMP to IMP with the release of 1 ammonia molecule, in purine metabolism. Normally, during vigourous exercise 2 ADP FORM 1 ATP AND AMP. And the AMP produced is converted to IMP by AMPD. Deficiency of AMPD leads to accumulation of AMP which [a] spills into blood where liver enzymes take up ribose and phosphate and lead to accumulation of adenosine in muscle [b] ATP Synthesis is determined by decreased ATP and incresed AMPD and hence leads to decreased ATP synthesis.

SINCE THE PT HAS BOTH G6P AND AMPD DEFICIENCIES THE SYMPTOMS TO OXIDATIVE STRESS AND DEPLETED ENERGY SUPPLIES ARE MORE SEVERE.


SYMPTOMATOLOGY AND DIAGNOSIS PERTAINING TO AMPD1 DEFICIENCY
  • Weakness, Fatigue, Muscle Pain,Intolerance to Exercise - Decreased Aerobic output and increased anaerobic output, Accumulation of adenosine in muscle fibres ,High level of lactate, Ammonia produced in the reaction is hypothesised for reduced fumarate available for Kreb's Cycle
  • Decreased And dark Urine After exercise/extreme stress -  Lactate elevation in blood. It could be because of Carb-Rich meals which lead to increased blood glucose. The glucose in blood is taken up by Muscles and Serum Lactate increases. And is excreted in the urine. Happens when load on muscles is greater than the body's ability to recycle it back to glucose. It could have been dark due to carbohydrates being excreted along with lactate in a concentrated form [my hypothesis, might be wrong]
  • Shortness of breath, Sudden waking up at night with palpitations - High glycemic index food leads to dumping of lactate  which leads to Tachypnoea, Delayed Gastric Emptying leading to Shock Lactic Acidosis leads to waking up at night with tachypnoea and palpitations
  • Migraine - Lactate in urine leads to obligatory excretion of Magnesium. Leading to Hypomagnesemia. HYPOMAGNESEMIA is associated with PALPITATIONS, DECREASED INTELLECTUAL ABILITY, MIGRAINES, etc
  • Anesthesia awareness - Anesthesia may lead to Malignant Hyperthermia in such patients and is contraindicated. 
  • Sleeping Issues - Hardly any REM sleep leads to anxiety, intellectual deficit, decresed immunity and increased oxidative stress. Adenosine accumulation in brain leads to feeling of fatigue and should promote sleep but since here NADPH is low [ G6PD] and Glycine is Low [non-essential AA which is an excitatory and inhibitory Neurotransmitter responsible for falling asleep] - there is sleep disturbance
  • Investigations 
  1. History 
  2. Ammonia levels post forearm execrcise - AMMONIA DOES NOT INCREASE IN AMPD1 DEF.
  3. Genetic Testing
TREATMENT

1. Ribose - orally, 0.2g/kg/day ; Taken hourly provides direct but limited source of energy to cells
2. Creatine Monohydrate
3. Cemitidine - Decreases swelling and Improves Sleep
4. L-serine - Improves Sleep Initiation and Maintenance
5. Triptans - Migraine 

OTHER MUTATIONS and PROBLEMS
  • MTHFR Mutation - Hyperhomocysteinemia which leads to increased risk of THROMBO-EMBOLIC EVENTS, Cognitive impairment and dementia, Increased Fractures in elderly
  • WNK1 Mutation - Hereditary sensory neuropathy  - reduced ability to feel pain, Dysregulation of Cation Chloride Cotransporters in Kidney 
  • VWF mutation - Heavy menstrual bleeding, Bruising
  • PCOS - Dysmenorrhea, Ectopic Pregnancy
  • Severe Infections of Kidney, Lungs
SYMPTOMS I COULD NOT REASON 
  • Stuttering, Loss of left side function 
  • High post meal cortisol
  • Discharge from Left Nostril
  • Vertigo like symptoms 
  • Excessive hair growth
  • Loss of vision 
MY EXPLANATION TO HER SYMPTOMS WITHOUT KNOWN HISTORY AND INVESTIGATIONS

 PATIENT CENTRED APPROACH
  1. SEVERE JAUNDICE AT BIRTH 
  • Hemolysis [SCD/ Thalassemia/ G6PD] 
  • Hemolytic disease of newborn/Rh Incompatility
  • AV Malformations/ Sepsis
  • TORCH infections/ Hep A/ Hep B
  • Alpha 1 anti-trypsin deficiency
     2. INTOLERANCE TO MILK / VOMITING POST FEEDING
  • Lactose Intolerance
  • Obstruction in the gut [Hypetrophic Pyloric Stenosis, Esophageal Atresia]
     3. DECREASED SLEEP SINCE BIRTH 
  • Inborn errors of metabolism
  • Congenital Heart disease
     4. DIFFICULTY IN BREATHING 
  • Severe anemia due to malnutrition and or hemolysis
  • Congenital heart disease
  • Asthma
  • Anxiety
     5. HIGH WITH FLUCTUATION DUE TO EDEMA 
  • Allergy
  • Kidney Disease
  • Hypothyroidsim
  • Hypoprotenemia - Hepatic Cause
  • Hemolysis 
     6. EXCESSIVE HAIR GROWTH 
  • Hyperandrogenism 
  • Hyperinsulinemia
  • Hypoinsulinemia 
  • Cushing's Syndrome
  • Precocious Puberty due to infections 
     7. HISTORY OF SEVERAL INFECTIONS OF LUNGS, KIDNEYS
  • Malnutrition 
  • Hyperglycemia
  • SCID
  • Chronic Granulomatous Disease
  • Multiple Myeloma 
  • Cystic Fibrosis
     8. SEVERE REACTION TO SULFA DRUGS AND ANTI MALARIAL AGENTS
  • Allergy
  • Hemolytic Anemia [G6PD/6PGD Deficiency]
  • Thrombocytopenia
  • Stevens-Johnson Syndrome
     9. FREQUENT FRACTURES
  • Anorexia
  • Kidney disease
  • Hormone related [ Cushings/ DM 1 or 2/ Adrenal Insufficency]
  • Lactose Intolerance
    10. FAVISM
  • Characteristic of G6PD Def. 
    11. INTOLERANCE TO EXERCISE
  • Anemia 
  • Cystic Fibrosis 
  • Fibromyalgia
  • Intracranial Hypertension
  • AMPD1 Def.
  • Cardiac Pathology
    12. SEVERE IMPAIRING HEADACHE
  • Migraine
  • Cluster Headache
  • Temporal Arteritis 
    13. VERTIGO
  • Migraine associated Vertigo
  • BPPV
  • Multiple Sclerosis
  • Tumours/Infarctions at Cerebellopontine Angle
   14. TRANSIENT LOSS OF VISION
  • Occlusion of vessel [CRAO/Ophthalmic Artery]
  • Giant Cell Arteritis
  • SLE
  • Migraine
  • Intracranial HTN
  • Intracranial Tumour
   15. SPONTANEOUS NASAL DISCHARGE
  • Cluster Headaches
  • Allergy
   16. WEAKNESS, NUMBNESS, FATIGUE OF LIMBS
  • Anemia
  • B12 and or Folate Deficiency
  • AMPD1 Def
  • Fibromyalgia 
DIFFERENTIAL DIAGNOSIS 
  • Chronic Granulomatous Disease
  • Severe Combined Immuno Deficiency Disorder
  • Multiple Myeloma
  • Multiple Sclerosis
  • McLeod Syndrome
  • G-6-PD Deficiency
  • 6-PGD Deficiency
  • APMD1 Deficiency
  • Cystic Fibrosis
  • SLE
  • Fibromyalgia
  • Cushings Syndrome
INVESTIGATIONS THAT MIGHT PROVIDE SOME INSIGHT
  • Complete Blood Picture, Complete Urine Examination
  • Hematocrit, Peripheral Smear, Reticulocyte Count
  • RBC Sickling Test, Hb Electrophoresis
  • Serum Iron, Ferritin, TBIC
  • Coombs Test - Direct, Indirect
  • Anti nuclear antibody test
  • LFT
  • RFT
  • Serum TSH, T3, T4
  • RBG, Insulin Levels
  • Serum FSH, LH, Estrogen, Progesterone, Prolactin, Testosterone
  • Cortisol 
  • Urine and Serum Electrolytes
  • Bone Mineral Density
  • Genetic Test
SOURCES



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