CASE 01 OF PARAPARESIS.

Presented by G. Mansa Shambhavi

Roll number 194.

8^th semester.

I have been given this case to solve in an attempt to understand the topic of Paraparesis.

The patient’s entire clinical data including history, clinical findings and other investigations is given below, followed by a visual discussion.

Click here for the patient's clinical data.

Click here for the visual discussion.

The chief complaints given by the patient:

Ø Weakness of bilateral lower limbs since 20 days.

Ø Edema of non-pitting type in bilateral lower limbs. (cardiomyopathy)

Ø Difficulty in squatting and getting up from squatting position. (proximal lower limb involvement)

Ø Difficulty in wearing and holding chappals. (distal lower limb involvement)

 

On examination,

o   General examination:

§  The patient was conscious, coherent and cooperative.

§  Moderately built and nourished.

§  No signs of pallor, icterus, cyanosis, clubbing, lymphadenopathy, edema.

o   Systemic examination:

Cardiovascular system:

§  S1, S2 heard.

§  No added murmurs.

Respiratory system:

§  Normal vesicular breath sounds heard.

§  Bilateral airway entry present.

Central Nervous System:

§  Cranial nerves: intact.

§  Motor system: normal tone, reflexes absent.

§  Sensory system: normal.

§  No meningeal and cerebellar signs.

The patient is observed to have a waddling or duck like gait, which occurs due to weakness of proximal muscles of the pelvic girdle. It is also known as Myopathic gait.

The patient is also observed to use Gower’s sign to get up to the standing position from squatting position. This indicates proximal muscle weakness (of hip and thighs).

Investigations:

·      CBP: Normocytic normochromic with leukocytosis.

·      CUE: Presence of albumin and pus cells is observed.

·      RFT: Increased levels of urea, creatinine and uric acid.

·      Muscle biopsy was conducted.

A Differential diagnosis of CIDP (Chronic Inflammatory Demyelinating Polyneuropathy), Polymyositis or muscular dystrophy was made.

The patient’s condition is considered to be a myopathy rather than a neuropathy due to the following differences:

MYOPATHY	NEUROPATHY
Associated with proximal weakness.	Associated with distal weakness.
Sensory involvement is not present.	Sensory involvement is present.
Motor involvement is seen.	Motor involvement is not seen.
Reflexes are preserved till late.	Reflexes are lost early.
Contractures may be present.	Fasciculations may be present.
May be associated with myocardial dysfunction or tenderness.	Cranial nerve involvement or autonomic dysfunction may be present.

 

Myopathies are neuromuscular disorders in which the primary symptom is muscle weakness due to dysfunction of muscle fiber.

Other symptoms of myopathy can include muscle cramps, stiffness, and spasm.

Myopathies can be inherited or acquired.

Ø Inherited Myopathies: Muscular dystrophies.

Ø Acquired Myopathies: Common muscle cramps.

The increased levels of creatine kinase and the muscle biopsy lead towards the probability of the condition to be a Muscular dystrophy and more likely, a Dystrophinopathy.

Muscular dystrophies are a group of diseases which cause increased weakening and breakdown of skeletal muscles, leading to an increased level of disability associated with atrophy (wasting).

Some types of muscular dystrophies may eventually affect the muscles of heart and respiratory muscles severely, making the condition sometimes Life threatening.

It is caused by mutations/changes in the genes which are responsible for the structure and functioning of a person’s muscles, which may cause changes in muscle fibers and lead to diminished ability of the muscles to function properly.

Muscular dystrophies are a group of 30 inherited genetic disorders mainly classified in 9 types:

o   Duchenne muscular dystrophy (Most common type).

o   Becker muscular dystrophy.

o   Congenital muscular dystrophy.

o   Distal muscular dystrophy.

o   Emery–Dreyfuss muscular dystrophy.

o   Facioscapulohumeral muscular dystrophy.

o   Limb-girdle muscular dystrophy.

o   myotonic dystrophy.

o   Oculopharyngeal muscular dystrophy.

In the above classification, Duchene muscular dystrophy and Becker muscular dystrophy are the possible (2 out of 4) dystrophinopathies that could be associated with the patient’s condition.

Duchenne muscular dystrophy (DMD):

It is an X-linked recessive inherited disorder characterized by progressive muscle degeneration and weakness caused due to the alterations of a protein called dystrophin that helps to keep the muscle cells intact and protects them from breaking down when exposed to enzymes.

In DMD, mutations in the genes may completely prevent the production of any functional dystrophin.

Becker muscular dystrophy (BMD):

It is an X-linked recessive inherited disorder characterized by muscle weakness, mainly in the legs and pelvis. It is slowly progressive.

It is caused by mutations in the dystrophin gene.

In BMD, the mutations in dystrophin gene lead to an abnormal version of dystrophin which retains some function.

(The provisional diagnosis was made to be BMD.)

Further investigations to confirm the diagnosis:

·      Electromyography.

·      Genetic testing. 

Treatment:

There is no known cure for muscular dystrophy.

Although, some measures can be taken to relieve some of the patient’s symptoms and maximize the patient’s quality of life.

§  Corticosteroids: increase muscle strength to an extent and delay progression of the condition.

§  Physical therapy: helps to maintain the muscle strength.

§  Medications to treat associated heart problems.

§  Surgery- to treat postural deformities.

§  Use of orthopedic support: braces to support weakened muscles. (ankle braces etc.)

§  Immunosuppresants: slow the progression of BMD.

§  Assisted ventilation: in patients where the disease affects the respiratory muscles.

Gene therapy.

References:

https://www.nhs.uk/conditions/muscular-dystrophy/

https://www.mda.org/disease/duchenne-muscular-dystrophy

https://www.mda.org/disease/becker-muscular-dystrophy

A case of a 42 year old woman with multiple health events since birth.

Presented by G. Mansa Shambhavi,

Roll number 194.

8th Semester.

I've been given this case to solve in an attempt to understand the topic of 'Patient clinical data analysis' to develop my competency in reading and comprehending clinical data including history, clinical findings, investigations and come up with a diagnosis and treatment plan.

You can find the patient's entire clinical problem in this link here:

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

My analysis of the patient's problems in order of priority are:

• Swelling, which is confined to face and abdomen.
• Migraine with aura.
• Weakness on the left side.
• Sleeplessness (reduced or absent REM sleep).
• Increased tolerance to pain.
• Oliguria.

An explanation to these symptoms based on the history is given below.

(01.) SWELLING:

The patient gave a history of swelling of face and abdomen from the age of 01 year, which continues till date.

Factors triggering swelling: Emotional stress, smoke, exercise, food like fava beans, medications like sulfur drugs, anti malarial drugs etc.

A plausible reason for this could be Haemolytic crisis due to G6PD deficiency, to which the patient was diagnosed last year.

G6PD deficiency is an X linked recessive disorder that causes glucose-6-phosphate dehydrogenase enzyme to be inadequate in blood. 

It is responsible for keeping the red blood cells healthy. 

It is also a very important enzyme that regulates various biochemical reactions in the body. 

Without adequate levels of this enzyme, breakdown of red blood cells occurs. 

It can be triggered by infections, stress, foods like fava beans etc. 

The early breakdown of red blood cells is called Haemolysis. This kind of early breakdown of RBCs eventually leads to Haemolytic anemia, which occurs when red blood cells break down faster than the body can replace them.

Edema in G6PD deficiency: Deficiency of G6PD leads to inadequate levels of NADPH and ATP which leads to excessive loss of ions and disturbed water balance, which leads to Edema. 

It also causes damage to the kidneys due to NADPH deficiency which causes free radical damage.

Also, as Haemolysis leads to decreased red cell count and reduced oxygen flow to the organs, it causes fatigue, shortness of breath and pale discolouration of skin.

Treatment:

• Avoiding the factors triggering stress.
• Consuming food which has good antioxidant properties.
• Drugs: the patient has been taking Cimetidine 400mg which has markedly reduced the frequency of episodes.
• Oxygen therapy.
• Blood transfusion in severe cases.

(02.) MIGRAINE:

The patient gave a history of severe headaches which began at the age of 02 years old, became very severe around the age of 14 with menses. The episodes became more severe over time.

Eventually, with severe attacks of migraine, her aura intensified and it even lead to loss of vision.

Investigations: Ophthalmoscopic examination, CT and MRI scan.

Treatment:

• Triptans ( 5HT 1B/1D).
• Dihydroergotamines.
• Antiemetic drugs (Ondansetron)
• Intranasal Ketamine reduces the duration of aura symptoms.
• Erenumab, which targets the calcitonin gene related peptide receptor.

(03.) WEAKNESS ON THE LEFT SIDE:

The patient gave history of left sided weakness occurring in the form of frequent falls on the left side and an unbearable feeling of spinning when turning to the left side in sleep. 

She experienced numbness of left hand and left side of face (as if someone was pouring cold water on her cheek)  during migraine attacks.

Diagnosis:

This could be probably occurring due to muscle weakness caused by AMPD1 deficiency (Adenosine Monophosphate Deaminase-1-Deficiency), or it could also be due to Haemiplegic Migraine.

Investigations: Complete neurological examination.

Treatment: Although there is no cure for AMPD1 deficiency, the use of d-Ribose might provide an additional source of energy to the muscles, though for a short term.

For haemiplegic migraine, NSAIDs and antiemetic medication provide symptomatic relief. Intranasal Ketamine reduces the duration of aura symptoms.

(04.)SLEEPLESSNESS:

The patient has had sleep disturbances from the time she was 01 year old.

She said that she could never sleep for more than 2-3 hours a day; with very reduced or almost absent REM sleep.

Diagnosis: This could be due to G6PD or AMPD1 deficiency.

• Low glycine levels in G6PD deficienchy could cause sleep disturbances.
• Adenosine is an inhibitory neurotransmitter which induces sleep. Therefore, AMPD1 deficiency causes sleep disturbances.

Treatment: L serine. it helps in inducing sleep.

(05.) INCREASED TOLERANCE TO PAIN:

The patient gave history of increased tolerance to pain from the age of 04 years, 

which has increased so much that she cannot even localize the pain now.

The probable diagnosis could be CIPA (Congenital Tolerance to Pain with Anhidrosis), which is caused by NTRK1 gene mutation.

Investigations: Genetic testing for CIPA (NRTK1 gene mutation).

(06.) OLIGURIA:

The patient gave history of decreased urination, which increases during fasting.

This could be due to deficiency of NADPH and ATP caused by G6PD deficiency which cause increased loss of ions.

REFERENCES:

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

(ii) https://en.wikipedia.org/wiki/Glucose-6-phosphate_dehydrogenase_deficiency

(iii) https://en.wikipedia.org/wiki/Erenumab

(iv) https://en.wikipedia.org/wiki/Adenosine_monophosphate_deaminase_deficiency_type_1

(v) https://ghr.nlm.nih.gov/condition/congenital-insensitivity-to-pain-with-anhidrosis