Paraparesis case study- 2


               An interesting case of an 18 year old male with paraparesis 


                                        Presented By: Simran Dash 
                                        MBBS- IV | Roll number: 153

I have been given this case data here:

https://srianugna.blogspot.com/2020/05/hello-everyone.html

                                My analysis for the above patient:

Age : 18 years

Chief complaints of the patient are :
       1) Weakness of both the lower limbs
       2) Bilateral non pitting edema of both lower limbs 

  1. Paraparesis:
  • Onset : Sudden
  • Duration : Since 1 year (Increase in the intensity since 2 months )
  • Progression : Gradually progressive (started in proximal region and then progressed to distal region) 
  • Associated features : 
                 a)Difficulty in getting up from squatting position (suggestive of proximal muscle weakness)
                 b) Difficulty in wearing and holding chappals.

From the history I am of the opinion that the possible differentials can be :
  1. Bilateral non pitting Edema :
            - Lymphoedema
            - Myxoedema 
     2.  Difficulty in getting up from squatting position suggests that the problems could be in the following sites :
            - Arthritis of knee joint ( but it occurs in older people)
            -  Muscles of legs, thigh or buttocks ( in arthritis of knee joint there is significant wasting of the muscles of things like Quadriceps femoris)
            - Muscles of arms
            - Cerebellar disorders 

On CNS examination :

           - Mild hypotonia in both the lower limbs ( 4/5 )
           - Reflexes are absent. 
           - Hypertrophy of the calf (gastrocnemius)muscles.         

On CVS Examination:

            - Muffled heart sounds suggestive of pericardial effusion.
            
Investigations done on this patient are :

          - CBP : 
                       Leukocytosis
                       Mild lymphocytisis
          - RFT:
                      Elevated urea
                      Elevated creatinine 
                      Elevated Uric acid
                      Elevated phosphorus levels
                      Decrease in Chloride levels 
            - CUE : 
                      Hypoalbuminemia
                      Pus cells 

            - ECG : large biphasic QRS complexes in V3,V4 leads. Suggestive of katz- Wachtel phenomenon. This indicates Left ventricular Hypertrophy 
            - ECHO : confirmed Hypertrophy of LV and RV
            - Muscle biopsy : showed dystrophy 
            - Serology : negative for HIV, Hepatitis B


So from the above I am of the opinion that:

Anatomical location of the root cause could be in the proximal muscle because:
         - Difficulty in getting up from squatting position.
         - Elevated Creatinine levels
         - Muscle biopsy confirmed dystrophy.

Microbiological cause for the non pitting Edema could be:
         Filariasis 

Pathological cause for this problem could be:
          - Genetic 
          - Endocrinological
          - Inflammatory 

Biochemical cause :
           - Mutations in the DMD gene which is responsible for the protein dystrophin. This protein helps stabilize and protect muscle fibers and may play a role in chemical signaling within cells. Mutations lead to an abnormal "version" of dystrophin. Muscle cells without fully functional dystrophin become damaged as muscles contract and relax with use. They then weaken and die over time, leading to the muscle weakness and heart problems in people with BMD (Becker’s muscular dystrophy).

Differential diagnosis on the basis of this :
  1. Becker’s muscular dystrophy 
  2. Hoffman’s syndrome- Clinical features in the patient suggestive of Hoffman’s syndrome are :
             a) Proximal muscle weakness
             b) Hypertrophy of calf muscles
             c) Dilatation of the heart
             d) Difficulty in getting up from squatting position and climbing stairs
   3. Duchenne muscular dystrophy  
   4. Chronic Inflammatory Demyelinating Polyneuropathy (is characterised by relapses)
   5. Polymyositis 
   
         
Additional examinations and investigations required to confirm the diagnosis:

  1. Genetic studies for DMD and BMD
  2. Thyroid profile - for Hoffman’s syndrome. It reveals Hypothyroidism 
  3. CPK levels ( Creatinine Phosphokinase ) - generally elevated in muscle diseases 
  4. Chest X ray to confirm the ECHO findings of LV Hypertrophy and Dilatation of heart 
  5. Tests of Cerebellar dysfunction should be done because Cerebellum helps in maintaining balance.
  6. EMG ( Electromyography ) - remains silent in Hoffman syndrome 
  7. Gait should be checked -
                a) Scissoring gait - upper motor neurone disease 
                b) Walking and suddenly knees are giving away - Lower motor neurone disease 

Treatment received by him: 
  1. T Prednisolone 15mg po od
  2. T Pantop 40mg bbf
  3. T Met xl 12.5mg od
  4. Cap Becosules od
  5. T Chymoral forte od
  6. T Taxim 200mg bd
  7. T Vit c od
  8. T Ultracet sos

Additional treatment required :

  1. For DMD:

            a) There is no known cure for Duchenne muscular dystrophy (DMD). Treatment is based on controlling  the symptoms of DMD and related complications caused by severe progressive muscle weakness and loss.        
            b) Steroids may improve the strength and function of muscles.
            c) An enlarged, weakened heart (dilated cardiomyopathy) may be treated with medications, but in severe cases, a heart transplant may be necessary. 
            d) Assistive devices for breathing difficulties may be needed, especially at night and as the disease progresses.

      2. For BMD:

            a) There is no known cure for Becker muscular dystrophy (BMD). Treatment is based on controlling  the symptoms 
            b) Affected people are encouraged to remain active.
            c) Potential future treatments for BMD may include 
                        gene therapy,
                        exon skipping, 
                        creatine, 
                        myostatin inactivation
                        cell therapy (myoblast treatment, and/or the use of stem cells)

    3. For Hoffman’s syndrome : Thyroxine 200 micrograms per day 

    4. Polymyositis: 

               a) Corticosteroids 
               b) Rituximab
               c) Physical exercise to improve muscle strength 




REFERENCES :

1) https://www.medicotips.com/2014/10/difficulty-in-standing-up-from-sitting.html?m=1

2) https://louisvillebones.com/pitting-edema-non-pitting-edema/

3) https://www.ncbi.nlm.nih.gov/books/NBK519513/

4) https://rarediseases.info.nih.gov/diseases/5900/becker-muscular-dystrophy

5) https://litfl.com/katz-wachtel-phenomenon/

6) Clinical methods of medicine by Arup kumar Kundu

7) Hutchison’s clinical methods

8) Davidson's principles and practice of medicine

 ACTIVE LEARNING POINTS:

20/05/20, 8:50:21 PM] MBBS 2016 UG 2: Good evening sir

[20/05/20, 8:51:38 PM] MBBS 2016 UG 2: Sir I wanted to ask regarding the ECG in the 1st case by Anughna ma’am. It’s not clear.

[20/05/20, 8:58:41 PM] Post Residency PG1: 👍yes please ask and also post your queries to the comment section of her log book and keep your queries coming as its the only way to score more and more learning points 👍

[20/05/20, 8:59:14 PM] MBBS 2016 UG 2: Okay sir

[20/05/20, 8:59:48 PM] MBBS 2016 UG 2: So what are the ECG findings?

[20/05/20, 9:00:21 PM] Post Residency PG1: Can you share a link to the Ecg image?

[20/05/20, 9:00:32 PM] MBBS 2016 UG 2: Yes sir

[20/05/20, 9:00:39 PM] MBBS 2016 UG 2: It is actually a picture

[20/05/20, 9:00:44 PM] MBBS 2016 UG 2: And it’s not very clear

[20/05/20, 9:01:13 PM] MBBS 2016 UG 2: But I heard the discussion where you have been saying that there is something in the V3 and V4 leads.

PHOTO-2020-05-20-21-01-36.jpeg
[20/05/20, 9:01:40 PM] Post Residency PG1: If you click on the picture it will open and you can copy the link from the browser

[20/05/20, 9:04:32 PM] Post Residency PG1: Share the link as all our discussion will go here too https://medicinedepartment.blogspot.com/2020/05/frequently-asked-questions-around-case.html?m=1

[20/05/20, 9:07:41 PM] MBBS 2016 UG 2: I did it sir.

[20/05/20, 9:08:03 PM] Post Residency PG1: Where?

[20/05/20, 9:08:29 PM] MBBS 2016 UG 2: In this link I copied the link and asked the question in the comments section

[20/05/20, 9:09:48 PM] Post Residency PG1: It's not showing. Anyway share it here

[20/05/20, 9:10:00 PM] MBBS 2016 UG 2: https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEhI6nJkokncACQxQOQecvfHUtP-6PIKJdU7IyFvTuswi3iXO5H0VnT9BOeIfLZeWgwBIEoBKTdKiGj4WrfnbsSp70axUaFfirpkbnCCNGhYMmkU7t1TVWpR0E9DVTTqkNYhUxpdvl4WWE-w/

[20/05/20, 9:10:54 PM] MBBS 2016 UG 2: It says the comment has to be approved.

[20/05/20, 9:11:13 PM] MBBS 2016 UG 2: It will be visible after approval sir

[20/05/20, 9:14:16 PM] MBBS 2016 UG 2: Okay sir. Thank you sir.

[20/05/20, 9:14:54 PM] Post Residency PG1: Is the voltage in the chest leads normal?

[20/05/20, 9:16:34 PM] MBBS 2016 UG 2: Yes sir.Actually it’s not very clear sir.

[20/05/20, 9:41:56 PM] Post Residency PG1: Are they similar to the EcGs described here?

https://litfl.com/katz-wachtel-phenomenon/

[20/05/20, 9:43:38 PM] MBBS 2016 UG 2: Yes sir.! It is similar to this

[20/05/20, 9:44:42 PM] Post Residency PG1: So what could your patient be having in his heart? Ask Anughna in her logbook comment box?

[20/05/20, 9:45:04 PM] MBBS 2016 UG 2: Yes sir I will ask Anughna maam

[20/05/20, 9:45:16 PM] MBBS 2016 UG 2: is it associated with a congenital heart disease?

[20/05/20, 9:47:52 PM] Post Residency PG1: What were the cardiovascular findings documented by Anughna?

[20/05/20, 9:48:42 PM] MBBS 2016 UG 2: I am asking ma’am sir. Dilatation of heart

[20/05/20, 10:05:25 PM] Post Residency PG1: So the Echo confirms the biventricular hypertrophy seen in the ECG?

[20/05/20, 10:06:50 PM] MBBS 2016 UG 2: Yes sir In the discussion video you said so.

[23/05/20, 4:26:33 PM] Post Residency PG1: You didn't mention what were the muscle biopsy findings in our patient and what are the possible muscle biopsy findings that you shared as differentials. 

The muscle biopsy was our only hope of clinching the pathology before we moved to another differential that would have necessitated a Biochemical study of the muscle tissue.

So what could be the biochemical causes of his myopathy?

[23/05/20, 4:29:58 PM] MBBS 2016 UG 2: Oh yes. I mentioned it saying the muscle biopsy showed dystrophy sir.

[23/05/20, 4:31:43 PM] MBBS 2016 UG 2: Hoffman’s syndrome sir. Hypothyroidism could be responsible for it. Because he also has Dilatation of LV

[23/05/20, 4:32:04 PM] MBBS 2016 UG 2: And his ECG findings also suggested that.

[23/05/20, 4:33:01 PM] MBBS 2016 UG 2: Biochemical cause could be the mutation sir. If he has Beckers, then he will have mutations in the dystrophin gene.

[23/05/20, 4:47:20 PM] Post Residency PG1: Did our patient have any findings in his muscle biopsy suggestive of any of the diseases you mentioned?

[23/05/20, 4:48:44 PM] Post Residency PG1: Can enzyme muscle deficiencies due to AMPD 1 mutations like the online patient case,  lead to myopathy? What will be the biopsy findings in such cases?

[23/05/20, 4:49:28 PM] Post Residency PG1: What is more important than ECG in confirming LV dilation?

[23/05/20, 7:35:39 PM] MBBS 2016 UG 2: Echo is more confirmatory sir.

[23/05/20, 7:36:38 PM] MBBS 2016 UG 2: Sir according to the Reports he didn’t have dystrophy.

[23/05/20, 7:39:02 PM] Post Residency PG1: Yes it was normal. 

So find out which are the myopathies where the muscle biopsy appears normal

[23/05/20, 7:39:22 PM] MBBS 2016 UG 2: Okay sir. I will do that.

[23/05/20, 7:55:47 PM] MBBS 2016 UG 2: Sir generally muscle biopsies have a sensitivity rate of 85% in case of myopathies but has about 100% sensitive in case of NMJ disorders.
And it is also more sensitive in case of an infectious etiology

[23/05/20, 7:56:18 PM] MBBS 2016 UG 2: http://iv.iiarjournals.org/content/32/6/1647.full

[23/05/20, 8:03:32 PM] Post Residency PG1: Sensitivity rate of 85% for which disease?

[23/05/20, 8:18:45 PM] MBBS 2016 UG 2: Myopathies in general and in that it has a comparatively lower rate for congenital dystrophies

[24/05/20, 4:30:25 PM] MBBS 2016 UG 2: Yes sir it can lead to myopathy.
But it is characterised by exercise induced fatigue in general not just paraparesis

[24/05/20, 4:32:35 PM] Post Residency PG1: 👍any links?

[24/05/20, 4:33:29 PM] MBBS 2016 UG 2: https://rarediseases.info.nih.gov/diseases/547/adenosine-monophosphate-deaminase-1-deficiency

[24/05/20, 4:33:35 PM] MBBS 2016 UG 2: Yes sir

[25/05/20, 12:10:27 PM] MBBS 2016 UG 2: No sir his muscle biopsy findings didn’t contribute to any of my differentials

[25/05/20, 12:11:14 PM] MBBS 2016 UG 2: But since he had dystrophy and CVS symptoms I thought of the possible diagnoses

[25/05/20, 12:11:47 PM] MBBS 2016 UG 2: I confirmed it with intern ma’am that he had dystrophy.

[25/05/20, 8:30:59 PM] Post Residency PG1: 👍👏👏

[25/05/20, 8:31:20 PM] Post Residency PG1: 👍

[25/05/20, 11:26:43 PM] MBBS 2016 UG 2: Thank you sir.

[26/05/20, 8:28:38 AM] Post Residency PG1: What is the confirmation of his dystrophy?

[26/05/20, 3:00:13 PM] MBBS 2016 UG 2: I think based on clinical features sir. I will confirm it once again with her.

[27/05/20, 8:16:01 AM] MBBS 2016 UG 2: Good morning sir. It was confirmed based on the clinical features, Creatinine kinase levels. Because muscle biopsy is not very confirmative in a case of Becker’s muscular dystrophy. For further confirmation genetic testing is needed.

[27/05/20, 9:12:29 AM] Post Residency PG1: So is it Becker's dystrophy or Enzymatic myopathy such as Pompes?

[27/05/20, 9:56:01 AM] MBBS 2016 UG 2: I will find it out sir.

[27/05/20, 8:57:59 PM] MBBS 2016 UG 2: Sir as it is a glycogen storage disorder it will affect the liver too. He does not have any symptoms suggestive of liver involvement.
And also the age is more suggestive of Becker’s.

[27/05/20, 8:58:22 PM] MBBS 2016 UG 2: Also in pompes there is more respiratory involvement than skeletal muscle.

2939.pdf
[27/05/20, 11:23:06 PM] Post Residency PG1: No respiratory involvement in this case log

[28/05/20, 8:31:02 AM] MBBS 2016 UG 2: Sir muscle biopsy in our case didn’t show any findings consistent with pompe’s. PAS staining should be done to detect glycogen.

[28/05/20, 8:32:07 AM] Post Residency PG1: Leaving aside PAS staining that couldn't be done here are there other findings in muscle biopsy that could be suggestive?

[28/05/20, 9:09:50 AM] MBBS 2016 UG 2: No sir. There are no findings which are consistent with pompes disease. 
We could do blood assay to check the α-glucosidase activity.

[28/05/20, 9:15:07 AM] MBBS 2016 UG 2: Blood based assays are more sensitive than muscle biopsy sir

[28/05/20, 9:15:22 AM] MBBS 2016 UG 2: https://pubmed.ncbi.nlm.nih.gov/25085280/

[28/05/20, 9:20:38 AM] Post Residency PG1: But are they specific?

[28/05/20, 10:38:29 AM] MBBS 2016 UG 2: More specific than muscle biopsy sir

[28/05/20, 10:41:17 AM] MBBS 2016 UG 2: And further to confirm the diagnosis it should be followed by a second GAA enzyme activity assay in another tissue or GAA gene sequencing.

[28/05/20, 10:41:32 AM] MBBS 2016 UG 2: https://pubmed.ncbi.nlm.nih.gov/19533647/

[28/05/20, 11:47:18 AM] Post Residency PG1: Can you share some numbers with the study links to substantiate this?

[28/05/20, 4:09:40 PM] MBBS 2016 UG 2: Yes sir

ED01.pdf
[28/05/20, 4:11:14 PM] MBBS 2016 UG 2: As per this, it has a sensitivity of 90-100% and specificity of >99%

[28/05/20, 4:43:46 PM] Post Residency PG1: It appears to be a review article. Can you quote the reference which would have been the actual study that demonstrated the sensitivity and specificity?

[28/05/20, 5:32:59 PM] MBBS 2016 UG 2: Okay sir. I will find it out

[28/05/20, 5:35:51 PM] MBBS 2016 UG 2: https://pubmed.ncbi.nlm.nih.gov/18519449/


[28/05/20, 5:37:39 PM] MBBS 2016 UG 2: But this is for IOPD sir.

Comments

Post a Comment

Popular Posts