2. HISTORY
10 YEARS PTA
(+) sudden jerky movements while awake, (-) when asleep
(+) frequent episodes of Falls
(-) loss of consciousness
(-) personality changes
INTERIM
Jerks became disabling & increased in frequency
Can no longer ambulate or feed himself without assistance
(+) awkward wide based gait,
(+) progressive deterioration in cognition
(+) hearing impairment, and proximal muscle weakness
39 yo/male
Right-handed
from Tondo, Manila
CC: progressive myoclonic jerks and weakness
J.D.
3. PAST MEDICAL HISTORY
(-) Hypertension
(-) Diabetes
(-) Renal Disease
(-) Pulmonary tuberculosis
(-) History of trauma
4. PERSONAL/SOCIAL HISTORY
No data available
FAMILY HISTORY
(-) Hypertension/ Cancer/ DM /Stroke /Heart
disease /allergies
9th /12 siblings (9 males; 3 females)
4 male siblings – died from an undiagnosed
illness (infancy to adulthood)
undocumented crippling illness – older
brother; died a year after onset
Mother: 63 yo, married
(+) non-disabling foot drop developed
insidiously x 30-35 years;
(+) mild atrophy – R anterior leg muscles
4/5 MMT – UE - proximal muscles
3/5 MMT - R knee flexors & plantar flexors
6. PHYSICAL EXAMINATION
General
Survey
Awake, alert, not in cardio-respiratory distress
Vital Signs BP: 100/70 (UBP=100-110/70-80) HR: 80 bpm RR: 19 cpm T: 36.8˚ C
Skin dry, no active dermatoses
HEENT Pink palpebral conjunctivae, anicteric sclerae, no gross head lesions; trachea midline no
palpable cervical lymphadenopathies, no distended neck veins; no carotid bruits;
Chest/Lung symmetrical chest expansion, clear breath sounds, no rales, no wheezes
CVS apex beat 5th ICS LMCL, distinct S1 and S2, normal rate, regular rhythm
Abdomen flat, normoactive bowel sounds, soft, no masses/tenderness/previous surgical
scars/organomegaly
Extremities Grossly normal extremities, Full and equal pulses, no edema, no cyanosis, good capillary
refill
8. Cranial
Nerves
I No anosmia
II No ptosis, pupils: 3mm EBRTL, no visual field cuts, visual acuity: 20/70 OS and
20/200 OD.
Fundoscopy: (+) ROR, distinct disc margin, 2:3AV ratio, no hemorrhages, no
papilledema, no pigmentary changes
II, III Pupils= 3 mm, EBRTL and to accommodation
III, IV, VI Bilateral medial and superior rectus palsy
V Intact V1,V2,V3; (+) corneal reflex, bilateral
VII No facial asymmetry, can raise brow, frown, smile
IX,X Uvula midline with intact gag, equal palatal elevation
XI Good shoulder shrug
XII Tongue base midline
9. MOTOR EXAM/SENSORY EXAM/DTR
MMT: generalized muscle atrophy, frequent intermittent
generalized jerky movements of all extremities lasting for few
seconds.
Muscle power was graded 3 & 4 in the proximal & distal muscles of
all extremities respectively.
DTRs: Normoreflexive
Sensory: intact vibratory and position senses, negative Romberg’s
sign
10. CEREBELLAR/MENINGEAL/GAIT
Cerebellars: No nystagmus, scanning speech, bilateral dysmetria,
dysdiadochokinesia, clumsy heel to knee-shin test
Meningeals: Supple neck, No Brudzinski/Kernig’s signs
Gait: He was unable to stand or walk without support. Marked
ataxia with broad based gait and inability to perform tandem walk
were observed.
11. DIAGNOSTICS
Total creatine kinase Mildly elevated at 378.3 IU
Pure tone Audiometry Moderate bilateral sensory neural hearing
loss
Interictal EEG Presence of pseudoperiodic delta waves
ECG Atrial enlargement and sinus tachycardia
EMG/NCV Myopathic changes were seen
Cranial CT scan Normal
12. SALIENT FEATURES
39 | M, no known comorbidities,
progressive myoclonic jerks and
weakness
Ten year history: sudden jerky
movements while awake -> became
disabling and more frequent ->
wide based gait -> progressive
deterioration in cognition, hearing
impairment, and proximal muscle
weakness
Family history: 4 males died from an
undiagnosed illness (infancy to late
adulthood) and mother had non-
disabling right foot drop
Impaired cognition, attention span,
and immediate memory
CN II - VA 20/200 OD
CN III, IV, and VI - bilateral medial
and superior rectus palsy
MMT: generalized muscle atrophy,
frequent intermittent generalized
jerky movements; ⅗ in proximal
muscles, ⅘ in distal muscles
Gait: Unable to stand or walk
without support; Marked ataxia with
broad based gait and inability to
perform tandem walk
No apraxia, no agnosia
Other cranial nerves are intact
Intact cerebellar: no nystagmus,
scanning speech, dysmetria,
dysdiadochokinesia, heel to knee
shin test
Normoreflexive
Supple neck, no Babinski/Kernig
Intact vibratory and position senses,
Negative Romberg
13. 39 | M, no known comorbidities,
progressive myoclonic jerks and
weakness
Ten year history: sudden jerky
movements while awake -> became
disabling and more frequent -> wide
based gait -> progressive deterioration
in cognition, hearing impairment, and
proximal muscle weakness
Family history: 4 males died from an
undiagnosed illness (infancy to late
adulthood) and mother had non-
disabling right foot drop
IS THERE A LESION?
Impaired cognition, attention span, and
immediate memory No apraxia, no
agnosia
MMT: generalized muscle atrophy,
frequent intermittent generalized jerky
movements; ⅗ in proximal muscles, ⅘
in distal muscles
Intact vibratory and position senses,
Negative Romberg
Gait: Unable to stand or walk without
support; Marked ataxia with broad
based gait and inability to perform
tandem walk
CN II - VA 20/200 OD
CN III, IV, and VI - bilateral medial and
superior rectus palsy
CN VIII - moderate bilateral
sensorineural hearing loss (PTA)
Other cranial nerves are intact
Cerebellar: scanning speech, dysmetria,
dysdiadochokinesia, clumsy heel to
knee shin test
Normoreflexive
Supple neck, no Babinski/Kernig
14. UMN OR LMN?
Impaired cognition, attention span, and immediate
memory
CN II - VA 20/200 OD CN III, IV, and VI - bilateral medial
and superior rectus palsy
CN VIII - moderate bilateral sensorineural hearing loss
(PTA)
Cerebellar: scanning speech, dysmetria,
dysdiadochokinesia, clumsy heel to knee shin test
MMT: generalized muscle atrophy, frequent intermittent
generalized jerky movements; ⅗ in proximal muscles, ⅘
in distal muscles
Gait: Unable to stand or walk without support; Marked
ataxia with broad based gait and inability to perform
tandem walk
16. Legally blind on the right eye, deaf bilaterally, eyes are out and
down
WHERE IS THE
LESION?
Impaired cognition, attention span, and immediate memory
17. Legally blind on the right eye, deaf bilaterally, eyes are out and
down
WHERE IS THE
LESION?
Impaired cognition, attention span, and immediate memory
MMT: generalized muscle atrophy, frequent intermittent generalized
jerky movements; ⅗ in proximal muscles, ⅘ in distal muscles
18. Marked ataxia with broad based gait and inability to perform tandem
walk
Legally blind on the right eye, deaf bilaterally, eyes are out and
down
WHERE IS THE
LESION?
Impaired cognition, attention span, and immediate memory
MMT: generalized muscle atrophy, frequent intermittent generalized
jerky movements; ⅗ in proximal muscles, ⅘ in distal muscles
23. Sudden jerky movements of all extremities
observed while awake, lasting for few seconds,
disappeared during sleep
Jerks were not associated with loss of
consciousness or personality changes
Resulted in frequent falls and became disabling
& more frequent = poor ADLs (ambulate and
eating)
Frequent intermittent generalized jerky
movements
WHERE IS THE MYOCLONUS COMING FROM?
24. WHERE IS THE MYOCLONUS COMING FROM?
Sudden jerky movements of all extremities
observed while awake, lasting for few seconds,
disappeared during sleep
Jerks were not associated with loss of
consciousness or personality changes
Resulted in frequent falls and became disabling
& more frequent = poor ADLs (ambulate and
eating)
25. WHERE IS THE MYOCLONUS COMING FROM?
Sudden jerky movements of all extremities
observed while awake, lasting for few seconds,
disappeared during sleep
Jerks were not associated with loss of
consciousness or personality changes
Resulted in frequent falls and became disabling
& more frequent = poor ADLs (ambulate and
eating)
26. WHERE IS THE MYOCLONUS COMING FROM?
Sudden jerky movements of all extremities
observed while awake, lasting for few seconds,
disappeared during sleep
Jerks were not associated with loss of
consciousness or personality changes
Resulted in frequent falls and became disabling
& more frequent = poor ADLs (ambulate and
eating)
27. WHERE IS THE MYOCLONUS COMING FROM?
Sudden jerky movements of all extremities
observed while awake, lasting for few seconds,
disappeared during sleep
Jerks were not associated with loss of
consciousness or personality changes
Resulted in frequent falls and became disabling
& more frequent = poor ADLs (ambulate and
eating)
28. WHERE IS THE MYOCLONUS COMING FROM?
Sudden jerky movements of all extremities
observed while awake, lasting for few seconds,
disappeared during sleep
Jerks were not associated with loss of
consciousness or personality changes
Resulted in frequent falls and became disabling
& more frequent = poor ADLs (ambulate and
eating)
29. Cranial CT scan normal
WHERE IS THE
FRIGGING LESION?
Cranial CT scan normal; Abnormal EEG: pseudoperiodic delta waves
EMG/NCV - Myopathic changes were seen
Total creatine kinase was mildly elevated at 378.3 IU.
32. DIFFERENTIAL DIAGNOSIS
Patient’s pertinent data SMA Type IV Mitochondrial Myopathy
(MERRF)
Limb Girdle Muscular Dystrophy
HISTORY:
(+) progressive myoclonic jerks
- Became disabling and frequent
- Frequent episodes of falls
(+) progressive weakness
**proximal muscle weakness
(+) awkward wide based gait
(+) progressive deterioration in
cognition
(+) hearing impairment
Mildest form
Onset: adulthood
Relatively mild proximal
limb weakness
Myoclonus
Seizures
Ataxia
Muscle weakness
Dementia
Hearing loss
Predominantly proximal weakness
Cramps on exercise
Lordotic posture
Prominent calves
progressive wasting (atrophy) may
have difficulty standing from a
sitting position or walking up stairs
difficultly raising their arms over
their heads or carrying heavy objects
FAMILY HISTORY:
- 4 male siblings died from an
undiagnosed illness (infancy to
adulthood)
- Mother: non-disabling right foot
drop
- can begin in childhood,
adolescence or early
adulthood after a period of
normal development
- vary greatly between affected
individuals in the same family
- affects males and females in
equal numbers
Slowly progressive:
presenting from early childhood to
the start of the 3rd decade of life
affects males and females in equal
numbers
33. DIFFERENTIAL DIAGNOSIS
Patient’s pertinent data SMA Type IV Mitochondrial Myopathy
(MERRF)
Limb Girdle Muscular
PE/NEURO EXAM:
Impaired cognition, attention span and
immediate memory
CN II – VA 20/200 OD
CN III, IV and VI – (B) medial and
superior rectus palsy
generalized muscle atrophy,
frequent intermittent generalized jerky
movements of all extremities
MMT: 3/5 in the proximal muscles & 4/5
in distal muscles
scanning speech, bilateral dysmetria,
dysdiadochokinesia, clumsy heel to
knee-shin test
CN: intact
MMSE: intact
DTR: may be absent or
reduced
Sensory examination is
typically normal
tongue fasciculations
Cognitive impairment
Short stature
degeneration of the optic nerve
(optic atrophy)
altered sensation (pins-and-
needles or pain) from nerve
damage (peripheral neuropathy)
Cardiomyopathy
Contractures
Cardiac dilatation
Heart failure
GAIT: unable to stand or walk without
support.
Marked ataxia with broad based gait
inability to perform tandem walk
Ataxia, with wide-based gait waddling gait
34. DIFFERENTIAL DIAGNOSIS
Patient’s pertinent data SMA Type IV Mitochondrial Myopathy
(MERRF)
Limb Girdle Muscular
NO MUSCLE BX DONE
CK: mildly elevated
EMG-NCV: myopathic changes
Interictal EEG: abnormal due to
presence of pseudoperiodic delta
waves
ECG: Atrial enlargement and sinus
tachycardia
gene testing:
homozygous deletion of
the SMN1 gene
EMG: variable features of
motor loss consistent
with loss of motor
neuron function
Muscle biopsy: ragged-red
fibers
CK levels:
EMG-NCV: small polyphasic
motor units with early
recruitment consistent with a
myopathic process
EEG: generalized spike and
wave discharges with
background slowing, but
focal epileptiform discharges
may also be seen
Genetic testing: (+) A8344G
point mutation
Muscle biopsy: muscle fiber
degeneration, regeneration,
fiber splitting and fibrosis
CK levels: elevated
EMG: small amplitude
polyphasic motor units with
early recruitment
https://rarediseases.org/rare-diseases/merrf-
syndrome/
https://rarediseases.org/rare-diseases/limb-girdle-muscular-
Physical Medicine & Rehabilitation, Braddom, 5th
edition
36. MITOCHONDRIAL MYOPATHY (MYOCLONIC EPILEPSY WITH RAGGED-
RED FIBERS)
Signs & Symptoms
can begin in childhood, adolescence or early adulthood
after a period of normal development.
vary greatly between affected individuals in the same family
and between different families
Myoclonus:
distinguishing feature in MERRF
usually the first symptom
Other symptoms: seizures, ataxia, muscle weakness and
dementia.
Short stature, degeneration of the optic nerve (optic
atrophy), hearing loss, and altered sensation from nerve
damage are also common symptoms.
Cardiomyopathy and the heart rhythm abnormality are
frequently present.
CAUSES:
MERRF syndrome is caused by mutations in
mitochondrial DNA (mtDNA).
Mutations are inherited from the mother. An affected
mother will pass on the mutation to all her children, but
only her daughters will pass it on to their children.
Heteroplasmy
number of defective mtDNAs may be out-numbered by the
number of normal mtDNAs.
The uneven distribution of normal and mutant mtDNA in
different tissues can affect different organs in members of
the same family.
result in a variety of symptoms in affected family
members.
Affected Populations: affects males and females in
equal numbers.
https://rarediseases.org/rare-diseases/merrf-
syndrome/
Pfeffer G, Chinnery PF. Diagnosis and treatment of mitochondrial myopathies. Ann Med. 2013;45(1):4-16.
39. NERVE CONDUCTION STUDIES
Normal sensory nerve conduction studies
Low Compound motor action potential over
muscles with severe atrophy
De Lisa’s Physical Medicine and Rehabilitation Principles and Practice 6th Ed
(2019)
Electromyography and Neuromuscular Disorders: Clinical Electrophysiologic Correlations 3rd
40. NEEDLE EMG
Abnormal spontaneous activity (positive
sharp wave/fibrillation potentials)
Low amplitude, often polyphasic, brief-
duration potentials with voluntary
contraction
Early recruitment pattern
De Lisa’s Physical Medicine and Rehabilitation Principles and Practice 6th Ed
(2019)
Paganoni, S., & Amato, A. (2013). Electrodiagnostic evaluation of myopathies. Physical medicine and rehabilitation clinics of North America, 24(1),
41. ROLE OF ELECTRODIAGNOSTIC STUDIES IN THE DIAGNOSIS OF
MYOPATHIES
1. Exclude neuromuscular conditions that may mimic a myopathy
2. Provide EMG evidence of the presence of a myopathy (although EMG may be normal in the presence
of selected myopathic processes)
3. Characterize the myopathy
4. Identify target muscles for biopsy
Paganoni, S., & Amato, A. (2013). Electrodiagnostic evaluation of myopathies. Physical medicine and rehabilitation clinics of North America, 24(1),
42. SUGGESTED EDX PROTOCOL FOR THE ASSESSMENT OF A
SUSPECTED MYOPATHY
1. Routine NCS
At least one motor and one sensory conduction study from one upper extremity and one lower extremity
2. EMG
At least one proximal and one distal muscle from one upper extremity (eg, deltoid, biceps, extensor digitorum
communis, or first dorsal interosseous)
At least one proximal and one distal muscle from one lower extremity (eg, iliopsoas, vastus lateralis, tibialis
anterior, or gastrocnemius)
Thoracic paraspinals
Paganoni, S., & Amato, A. (2013). Electrodiagnostic evaluation of myopathies. Physical medicine and rehabilitation clinics of North America, 24(1),
43. DIAGNOSTIC TESTING IN MITOCHONDRIAL MYOPATHY
I. Testing to confirm the presence of dysfunction in various organ systems
II. Tests that definitely address whether the patient is affected by a mitochondrial myopathy
Muscle biopsy
Molecular genetics
Pfeffer, G., & Chinnery, P. F. (2013). Diagnosis and treatment of mitochondrial myopathies. Annals of
medicine, 45(1), 4–16.
44. Pfeffer, G., & Chinnery, P. F. (2013). Diagnosis and treatment of mitochondrial myopathies. Annals of
45. MUSCLE BIOPSY
Quadriceps femoris or deltoid
In general, the detection of any COX-deficient fibres in individuals <50 years of age, or a higher
frequency of COX-deficient fibres at any age (>5%), is strongly suggestive of a mitochondrial disorder.
Electron microscopy: enlarged pleiomorphic mitochondria and paracrystalline inclusions
Respiratory Chain Enzyme analysis
Pfeffer, G., & Chinnery, P. F. (2013). Diagnosis and treatment of mitochondrial myopathies. Annals of
medicine, 45(1), 4–16.
46. MOLECULAR GENETICS
mtDNA mutation - mosaic appearance of COX-negative fibres
nDNA mutation - uniformly decreased COX activity
MELAS harbouring m.3243A > G - presence of strongly succinate dehydrogenase-positive blood
vessels (SSVs)
Pfeffer, G., & Chinnery, P. F. (2013). Diagnosis and treatment of mitochondrial myopathies. Annals of
medicine, 45(1), 4–16.
47. OTHER DIAGNOSTIC TESTS
Skin biopsy – obtain fibroblasts for RCE and DNA for genetic studies
Liver biopsy – to exclude other disorders and is a tissue source for analysis
CoQ10 deficiency in muscle tissue, fibroblasts and white blood cells
Exercise testing with cycle ergometry or treadmill – controversial
Venous pO2 during handgrip testing – excellent specificity, non-invasive screening test for MM
Pfeffer, G., & Chinnery, P. F. (2013). Diagnosis and treatment of mitochondrial myopathies. Annals of
medicine, 45(1), 4–16.
48. MEDICAL TREATMENT
There is no specific treatment for MERRF, similar to other mitochondrial
disorders.
This condition cannot be cured.
Multiple therapeutic agents are tried to decrease the decrease progression
with variable results.
DiMauro S, Hirano M. MERRF. In: Adam MP, Ardinger HH, Pagon RA,
Wallace SE, Bean LJH, Stephens K, Amemiya A,
editors. GeneReviews® University of Washington, Seattle; Seattle (WA):
Jun 3, 2003
49. These therapeutic agents include coenzyme Q10 (CoQ), vitamin B-complex
supplementation, and L-carnitine
DiMauro S, Hirano M. MERRF. In: Adam MP, Ardinger HH, Pagon RA,
Wallace SE, Bean LJH, Stephens K, Amemiya A,
editors. GeneReviews® University of Washington, Seattle; Seattle (WA):
Jun 3, 2003
50. TOXINS AND PHYSIOLOGIC STRESS
Alcohol and Cigarettes
Inhibit complex IV of OXPHOS
Heat and Cold Stress
exposure to cold can result in severe heat loss and trigger an energy crisis
51. Physiotherapy guidance for people with mitochondrial disease
http://mitochondrialdisease.nhs.u
k/professional-area/care-
guidlines/
52.
53.
54.
55. FATIGUE
Provision of aids and adaptations to conserve energy when walking or performing daily life activities
Exploring individualized exercise interventions to optimize aerobic capacity.
Liaison with Occupational Therapists or Psychologists with experience in assessing and supporting
individuals to manage their fatigue.
Sleep studies to explore a person’s sleep.
58. EXERCISE TIPS/ADVICE:
Keep yourself hydrated and carry water with you when exercising.
Make sure you are well nourished (if diabetic check blood sugar before and after exercise).
Always start off with low intensity and duration.
Spread your training days evenly along the week and have rest days in between, trying to avoid sitting
still for too long on rest days.
59. A certain level of muscle soreness is to be expected after training (in
particular when we are new to a type of exercise). It should not be a
concern unless it lasts more than 48hrs.
If soreness lasts for over this time you have probably over done it. Whilst
exercising you should feel slightly out of breath, your heart rate should be
slightly higher and you should feel slightly warm BUT you should still be
able to hold a conversation.
Be aware if there are any changes to the colour of your urine after you
have done strenuous exercise. Black or ‘coca cola’-coloured urine can be a
sign of muscle damage (myoglobulinuria).
60. Complex and Varied
maintain function
prevent contractures, skin break down
reduce risk of aspiration.
maintain function and prevent
contractures, skin break down and reduce
risk of aspiration.
Orthotics and splinting
61. REHABILITATION
Aerobic exercises
Endurance exercises
Resistance
Jeppesen T.D., Schwartz M., Olsen D.B. Aerobic training is safe and
improves exercise capacity in patients with mitochondrial
myopathy. Brain. 2006;129:3402–3412
“ It is likely the benefits of exercise in
Mitochondrial Myopathy are due to reversal of
deconditioning, which is a common feature of
many muscle diseases. Furthermore- exercise
seems to alter the underlying pathology by
promoting mitochondrial biogenesis. ”
62.
63.
64.
65.
66. PROGNOSIS
MERRF is a chronic condition, which is slowly progressive. As explained above, different
individuals become symptomatic with different phenotypes and at different ages, even within
the same family. Hence, the exact prognosis is difficult to ascertain, but usually, it is poor.
67. FOLLOW UP
Affected persons with MERRF and their asymptomatic at-risk
relatives should have a regular follow-up (e.g., every 6 to 12
months initially) for disease monitoring and the appearance of new
symptoms.
It is recommended to have an annual neurologic, ophthalmologic,
cardiology, and endocrinologic evaluations to screen for
complications
68. T H A N K Y O U
Aral na guys~! End-of-module Exam next week
Hinweis der Redaktion
With muscle fiber injury, this enzyme leaks into the serum. Particularly high elevations (50 to 100 times the normal) of CK may be found in acute inflammatory myopathies and early DMD and BMD.
More slowly progressive dystrophies may have mild to moderate elevations of CK levels
Normal – congenital myopathies, slowly progressive dystrophies, chronic inflammatory myopathies, myopathies of systemic disease
Mildly elevated in normal individuals for several days after vigorous exercise
Pure-tone audiometry is broadly defined as either screening or threshold search. Screening audiometry presents tones across the speech spectrum (500 to 4,000 Hz) at the upper limits of normal hearing (25 to 30 dB for adults, and 15 to 20 dB for children).17 Results are recorded as pass, indicating that the patient's hearing levels are within normal limits, or refer, indicating that hearing loss is possible and a repeat screening test or a threshold search test is recommended.
Threshold search audiometry determines the softest sound a patient can hear at each frequency 50 percent of the time. This testing requires more time and expertise than screening audiometry.
Myopathies usually come with cardiac problems
The first step in localization in neurology is to determine whether it is an upper motor neuron or a lower motor neuron.
Medial rectus = turns the gaze medially
Superior rectus = turns the gaze upward
An impaired stance in the absence of motor weakness or gross involuntary movements is suggestive of cerebellar ataxia or sensory ataxia.
Sensory ataxia is mainly reflected by gait disturbance, as previously described. In addition, subjects with sensory ataxia will have a positive Romberg sign.
Stance. A healthy person can stand naturally with feet spread less than 12 cm apart and is able to stand stable with feet together or in tandem for more than 30 seconds.
4 males died from an undiagnosed illness (infancy to late adulthood) and mother had non-disabling right foot drop
Present condition started about 10 years prior to admission, as sudden jerky movements of all extremities observed while he was awake, lasting for few seconds, and disappeared during sleep. The jerks were not associated with loss of consciousness or personality changes, however, it resulted in frequent falls
Myoclonus is a sudden brief (20–250 ms) contraction (positive myoclonus), or a brief and sudden cessation of tonic muscle (negative myoclonus) inducing a simple jerky movement of body part. Myoclonus could have different origins in almost every part of the nervous system, from the cortex to the peripheral nerve, sharing a large panel of etiologies.
Clonus refers to a series of rhythmic, monophasic (i.e., unidirectional) contractions and relaxations of a group of muscles, differing in this way from tremors, which are always diphasic or bidirectional.
Myoclonus specifies the very rapid, shock-like contractions of a group of muscles, irregular in rhythm and amplitude, and, with few exceptions, asynchronous and asymmetrical in distribution.
Cortical myoclonus is the most common form of myoclonus, seen in both outpatient and inpatient clinical settings. Cortical myoclonus mainly affects the distal upper limbs and face, which reflects the largest cortical representations of these body areas [Caviness, 2009]. It is often focal, but may be multifocal, bilateral or generalized, as a consequence of intracortical and transcallosal spreading of abnormal activity [Brown et al. 1996, 1991a]. It typically occurs on voluntary action and may affect speech and gait. Cortical myoclonic jerks are stimulus sensitive, typically to touch, but sensitivity to visual stimuli is also described [Shibasaki and Neshige, 1987]. Most patients with cortical myoclonus have both positive myoclonus and NM, occurring either independently or together as a complex of the two kinds of myoclonus
Epileptic myoclonus (or myoclonic seizure) is defined as the association of myoclonic jerks with an epileptic discharge on EEG (polyspikes or spike/polyspike-wave).
Brainstem myoclonus is manifested by generalized jerks and its most striking clinical feature is sensitivity to auditory stimuli. Two main types are (i) startle response, which may be physiologic or pathologic (hyperekplexia), and (ii) reticular reflex myoclonus.
Spinal myoclonus may be segmental or propriospinal, reflecting spinal segmental organization and the presence of propriospinal pathways which connect different spinal segments [Brown et al. 1994]. It is generally resistant to supraspinal influences such as sleep (therefore it may persist in sleep) or voluntary action (therefore it is present at rest, independently of activation) and may or may not be stimulus sensitive [Caviness and Brown, 2004].
So we’re going to localize it here in the cortex but we’re still not convinced cos we said lower motor neuron
Going to be jumping the gun here but…
Interictal EEG is defined as an electroencephalographic recording that does not contain seizures or ictal manifestations and is therefore obtained in the intervals between clinical attacks
**proximal muscle weakness, manifested by: difficulty in getting up from a sitting position and difficulty raising arms above the shoulder level
SMA
Spinal muscular atrophy includes a group of genotypically and phenotypically diverse disorders associated with features of LMN loss
Some forms of SMA are associated with a distal predominant patter of weakness, and therefore have been described with the term distal SMA
Distal SMA or dHMN have clinical features of: distal weakness and atrophy, reduced to absent reflexes, sensory function, by definition is preserved
Although a potential manifestation of a MND is a painless foot drop (as manifested by the patient’s mother), the patient shows no other symptoms that are similar to MND or SMA and since the lesion is in the motor neuron
SMA
Spinal muscular atrophy includes a group of genotypically and phenotypically diverse disorders associated with features of LMN loss
Some forms of SMA are associated with a distal predominant patter of weakness, and therefore have been described with the term distal SMA
Distal SMA or dHMN have clinical features of: distal weakness and atrophy, reduced to absent reflexes, sensory function, by definition is preserved
Although a potential manifestation of a MND is a painless foot drop (as manifested by the patient’s mother), the patient shows no other symptoms that are similar to MND or SMA and since the lesion is in the motor neuron – cortical function, cranial nerves should be intact
Pseudoperiodic lateralized epileptiform discharges (PLEDs) are EEG abnormalities consisting of repetitive spike or sharp wave discharges that are focal or lateralized over 1 hemisphere, recur at intervals of 0.5-5 seconds, and continue through most of a routine EEG study.
General Discussion
an extremely rare disorder that begins in childhood and affects the nervous system and skeletal muscle as well as other body systems.
The distinguishing feature in MERRF is myoclonus, consisting of sudden, brief, jerking spasms that can affect the arms and legs or the entire body.
Signs & Symptoms
Symptoms of MERRF syndrome can begin in childhood, adolescence or early adulthood after a period of normal development.
Symptoms and physical findings associated with MERRF syndrome vary greatly between affected individuals in the same family and between different families. Myoclonus is usually the first symptom followed by seizures, ataxia, muscle weakness and dementia. Short stature, degeneration of the optic nerve (optic atrophy), hearing loss, and altered sensation (pins-and-needles or pain) from nerve damage (peripheral neuropathy) are also common symptoms. Cardiomyopathy and the heart rhythm abnormality known as Wolff-Parkinson-White syndrome are frequently present. Occasional symptoms include benign fat cell tumors (lipomas), especially around the neck, and eye abnormalities involving melanin in the retina (pigmentary retinopathy).
CAUSES:
MERRF syndrome is caused by mutations in mitochondrial DNA (mtDNA).
Mutations are inherited from the mother. An affected mother will pass on the mutation to all her children, but only her daughters will pass it on to their children.
Both normal and mutated mtDNA can exist in the same cell, a situation known as heteroplasmy. The number of defective mtDNAs may be out-numbered by the number of normal mtDNAs. Symptoms may not appear in any given generation until the mutation affects a significant proportion of mtDNAs. The uneven distribution of normal and mutant mtDNA in different tissues can affect different organs in members of the same family. This can result in a variety of symptoms in affected family members.
Affected Populations: MERRF syndrome is a rare disorder that affects males and females in equal numbers.
DIAGNOSIS:
based on clinical findings and molecular genetic testing
Clinical testing may include measurement of lactate and pyruvate concentrations in blood and CSF.
CSF protein may also be elevated in MERRF syndrome.
Electrocardiogram may be used to diagnose heart rhythm abnormalities.
Muscle biopsy will usually show ragged red fibers. (Abnormal muscle cells are present and appear as ragged red fibers (RRF) when stained with the modified Gomori trichrome and viewed microscopically. MERRF is caused by mutations in mitochondrial DNA (mtDNA))
EDX studies, however, are not always needed to diagnose a myopathy.
Electrodiagnostic studies can be extremely important in the evaluation of the patient with myopathy to localize the pathology to the muscle rather than nerve or anterior horn cell. However, electrodiagnostic studies in myopathy may be normal as well, so a myopathic disorder is not ruled out by normal EMG studies.
Nerve conduction studies should be normal in myopathic disorders
Dependent on whether the myopathy is causing active muscle fiber degeneration
Early recruitment pattern – excessive number of motor units for a given strength of contraction; these findings may be subtle or absent particularly in slowly progressive disorders
Paraspinal ,suprspinatus, infraspinatus, glutei, iliopsoas
> Does not confirm a diagnosis of MM. The tests selected are guided by the pattern of organ involvement in each individual patient.
Cytochrome C oxidase
From a limb muscle
The major diagnostic feature is the presence of fibres deficient for COX activity, which represents poor activity of complex IV of the respiratory chain
This testing must be done in fresh or snap-frozen muscle samples, difficult to perform even in specialist laboratories
RCE Complex I + III deficiency or complex II + III deficiency in CoQ10 deficiency
Based on muscle biopsy findings
MELAS – easily detected in the urine
However, the RCE defect or molecular genetic defect may not be present in fibroblasts in all patients, and as a result this method has lower sensitivity than muscle biopsy
Controversial – low specificity and sensitivity
Patients with MERRF are at increased risk for cardiac arrhythmia and ventricular dysfunction resulting in cardiac failure and sudden death. They are also at high-risk for head trauma due to seizures, respiratory complications, kyphoscoliosis, diabetes mellitus, and thyroid problems
Co factros
possibly enhance enzyme function and result in improved efficiency of energy generation
serve as antioxidants, which may slow the progression of the disease
None has demonstrated a striking efficacy in clinical trials, although numerous non-blinded studies and small series have suggested modest efficacy.
itamins and cofactors are compounds that are required in order for the chemical reactions, which make energy, to run efficiently. By definition, a cofactor can be made by the body, whereas a vitamin cannot, and therefore must be eaten. For most people, a regular diet contains all the vitamins one could possibly need and their bodies can make as much of any specific cofactor that it needs. For those with mitochondrial disorders, added vitamins and cofactors may be useful.
Although extremely rare, PMM caused by CoQ10 deficiency will sometimes respond to high dose of CoQ10 supplementation;
Alcohol has been know to hasten the progression of some mitochondrial disorders. Cigarette smoke, probably due to the carbon monoxide, is known to hasten the progression of some conditions. Remember that carbon monoxide kills by inhibiting complex IV of OXPHOS, why make it worse? Cigarette smoke will make it worse.
When going out into the cold, all exposed body parts should be covered, and exposure to extreme cold should be avoided for anything more than a short period. Over bundling can be a problem too
Patients should avoid direct sunlight on hot days and stay indoors if it is too warm outside. An air-conditioned environment may be needed.
s. Whilst only some of these difficulties can be directly addressed physiotherapy input, all should be considered in the development of each individual’s treatment plan.
pain is a common and complex complaint (Fig 4). It is important that the severity, irritability and nature of the pain are assessed and understood. Assessment should include possible: triggers for pain, aggravating and easing factors as well as a full biomechanical, postural and functional assessment to understand the potential causes of pain
Optimising and improving soft tissue length or alignment. Provision of aids. Strategies to help pace activity and plan rests in order to manage pain.
his can be done by either increasing general levels of habitual physical activity and/or starting a graded exercise program alongside methods of energy conservation.
A formal cardiopulmonary exercise test and measurement of lactate at rest and during exercise can help physiotherapists to
understand the exercise limitations of a patient and be beneficial in guiding exercise prescription
graded exercise program and/or an increase in day to day physical activity. Progression of exercise by increasing duration and/or intensity of exercise can be challenging and may require prolonged involvement from physiotherapy services.
It is recommended that each person with mitochondrial disease have his or her cardiac status (blood pressure, ECG +/- echocardiogram, MRI of the heart), serum lactate level, and diabetic status (blood sugar) checked prior to undertaking exercise
Ataxia is a term for a group of disorders that affect co-ordination, balance and speech. In this case due to problems with a part of the brain called the cerebellum, Early intervention aimed at maintaining function, preseving mobility and reducing the risk developing secondary complications associated with immobility, are likely to be the most beneficia
. Dystonia is more prevalent in children with mitochondrial disease and requires close liaison between medical staff, physiotherapists and tertiary neurodisability services to treat effectively
As with other causes of dystonia that resulting from mitochondrial disease requires a multi-modality approach with medications. Levodopa, Baclofen and Trihexyphenidyl being used alone, in combination or together with targeted botulinum toxin injections
It is likely the benefits of exercise in PMM are due to reversal of deconditioning, which is a common feature of many muscle diseases. Furthermore, in PMM exercise seems to alter the underlying pathology by promoting mitochondrial biogenesis.
Already developed exercise protocols for MM only include classic aerobic leg training on cycle or treadmill. However, most patients need and must do some form of lifting, carrying, or pushing activity in their daily routine. Including arms strength training as part of the patient’s normal exercise program will better prepare them to perform other strength tasks safely and more efficiently
They fulfilled all the clinical inclusion criteria stated for the study: (1) MM with exercise intolerance or active muscle pain; (2) limited exercise performance, with a degree of impaired VO2max in the maximal exercise testing established as 83% of predicted values, according to equations proposed for normal individuals by Wasserman et al.38; (3) absence of joint or bone deformities; (4) absence of cardiac and respiratory disease assessed by electrocardiogram, cardiac ultrasound scan, chest X-ray, and spirometry tests (FEV1/FVC was required to be 70%); and (5) absence of uncontrolled epilepsy
For three nonconsecutive days each week, patients combined cycle exercise at 70% of their peak work rate with three upper-body weight-lifting exercises performed at 50% of maximum capacity. Training increased maximal oxygen uptake (28.5%), work output (15.5%), and minute ventilation (40%), endurance performance (62%), walking distance in shuttle walking test (95 m), and peripheral muscle strength (32%– 62%), and improved Nottingham Health Profile scores (21.47%) and clinical symptoms
MERRF is a multisystem disease. It needs a team of specialists for optimal care. Affected persons with MERRF and their asymptomatic at-risk relatives should have a regular follow-up (e.g., every 6-12 months initially) for disease monitoring and the appearance of new symptoms.
It is recommended to have annual neurologic (epilepsy control), ophthalmologic (for vision changes), cardiology (electrocardiogram and echocardiogram), and endocrinologic evaluations (for diabetes and thyroid problems). Physiotherapy, occupational therapy, and rehabilitation are important for improving the quality of life and prevent complications