A complex case of proximal weakness
Analyzing the dynamics of patients’ access to a GP clinic, it is possible to rate the frequency of consultations: there are some patients going very rarely to their GP (one or less access in a year), and some others (so-called ” frequent attenders “) go several times within a few months.
Carelli Francesco , Professor for Family Medicine, University of Milan
Giotta Attilio, intern doctor FM, University of Milan
Ioni Barbara , intern trainee, University of Milan
Ferrario Guido , intern doctor, University of Milan
Among these last ones we can identify both chronically ill patients needing clinical controls and frequent checking, and those coming to the GP clinic because of a new-onset disease, which needs some diagnostic classification, some deeper study and investigation, some treatment… In these cases the trust relationship between the patient and his GP will be crucial and will result, moreover, in a very good compliance to recommendations, examinations and assessments essential for a correct diagnosis.
This was the situation in our GP clinic with a patient who came to us with an average frequency of about 3/4 visits per month , due to a disease with gradual onset and no familiarity: it was characterized by a proximal muscle weakness in all four limbs, at first involving lower ones, then upper ones. This condition was also associated with difficulty in walking, muscle soreness and cramps in the thighs.
As a first approach it was preferred to act on three fronts: blood tests, electromyography, and MRI of the spine. Because of the increasingly debilitating symptoms, the patient performed the tests in a very short time, and the task of the GP was as well to solicit these tests and to explain why these tests were so important, as to provide reassuring answers on the symptoms reported by the patient.
The blood tests showed: abnormally high CPK (1897 IU /l, with reference values usually between 10 and 70); CRP=13.5 mg/dl; in SPEP monoclonal peak in the γ-zone with negative immunofixation. EMG showed signs of bilateral neuropathic radicular suffering at L4, C5, C6 level and myogenic suffering of the proximal muscles examined, while MRI showed a diffuse mild spondylosis , with likely contact between the disc and the root at the level of L3/L4. Considering clinical history and examinations results, while waiting for neurological consultation, the GP decided to start a therapy with prednisone 25 mg, 2 tablets per day, which resulted in a clear benefit on painful and cramping symptoms. During neurological consultation, it was raised the possibility of a paraneoplastic syndrome, to be confirmed by biopsy of the left deltoid muscle . The patient was very worried about that, because he did not receive clear and comprehensive answers regarding his symptoms by the specialist, and so he relied to his GP to get clarification on it. This need for further explanation arose from the fact that the recommendation of deltoid biopsy implied also hospitalization in the neurology department for several days, to complete all the necessary investigations needed to shed light on the causes of the symptoms, which at that time were becoming highly disabling because of the effects on walking.
First neurological evaluation at admission in Neurological Department of the Hospital showed no involvement of cranial nerves; segmental weakness in the biceps and triceps brachialis, with atrophy in the upper limbs; segmental weakness of ileum-psoas and atrophy of quadriceps femoris, all associated with autonomous walking with caution, easy on the tips and with some difficulty on the heels. During the hospitalization a biopsy of the deltoid muscle was performed, after discontinuing steroid therapy, which led to a renewed increase of CPK, fact that has not been investigated during the same hospitalization. The assessment revealed a situation of inflammatory muscle suffering, namely the muscle fibers were characterized by variability in size: with numerous fibers, also markedly hypotrophic, alongside other normal or increased in size; some in a state of necrosis, sometimes with invasion of macrophage or with small inflammatory infiltrates around the fibers, associated with rare regenerating fibers. In the assessments carried out during the period of hospitalization, it was found macrocytosis and enhancement of anti-thyroglobulin antibodies (anti-Tg). This latter test has led to a thyroid ultrasound followed by an endocrinological assessment and a subsequent diagnosis of Hashimoto’s chronic thyroiditis. Because of the suspicion of a paraneoplastic syndrome by the neurologist, the patient has performed a total body CT scan, negative for tumor lesions, but showing some lung emphysematous bubbles . For this reason, the patient underwent pneumology visit, assessment of lung function and Mantoux test (then found negative).
The patient was then discharged with a diagnosis of hyper-CK-emia in assessment, and with recommendation for continuing prednisone as suggested by the GP, associated with omeprazole as gastroprotective.
The patient went then to update his GP about the evolution of his symptoms, and also to let him know about what emerged from the hospitalization, and to have clarification on the prognosis. The disease has required chronic use of prednisone because, at any attempt of discontinuation of the therapy, symptoms and increase in CPK, constantly monitored, recurred spontaneously. The patient is still receiving treatment, with scheduled neurological controls every two months, and now he goes on a regular basis to update his GP about the symptoms, the specialist’s visits and the evaluation of CPK ( where the increase is based on inflammation, but the cause remains to be determined) but also for the prescription of therapy.
A deepening on hyper-CK-emia
Creatinephosphokinase (CPK) ,former name of creatinekinase (CK), is an activated enzyme of the transferase class that catalyzes the phosphorylation of creatine by ATP to form phosphocreatine.
The reaction effectively stores the energy of ATP as phosphocreatine in muscle and brain tissue and holds the muscle concentration of ATP nearly constant during the initiation of exercise.
There are three isozymic forms of serum CK: MM (skeletal muscle), BB (central nervous system) and MB (cardiac muscle) can be measured, although there is only an increase in MM and BB isozymes in muscle degeneration and regeneration. 1.
In all the diseases causing a damage of muscle fibers there is a blood release of enzymes such as aldolase, lactic dehydrogenase, transaminase (AST), but the enzyme more indicative of muscle destruction is CK, especially in case of acute process, even if in some cases it may not be high.
This is especially true in children with dermatomyositis (DM) not treated although active, in patients with forms of DM and polymyositis associated with connective tissue disease, reflecting the concentration of the disease process in intramuscular vessels, in perimysium, and even in patients with degenerative muscle diseases, where muscle mass has been however already depleted by illness. 3.
In other cases, for example in hypothyroidism, CK is high although there is no necrosis, or in non-pathological situations such as after using the needle of EMG, which can often cause a rise in serum levels of the enzyme for 2 -3 days (it is better always to obtain laboratory data before the EMG).
To determine the origin of CK (muscle, heart, central nervous system), it is possible to use quantitative assessment of the various muscle isoenzymes . MM isoenzymes of CK are present in greater amounts in striated muscle: in patients with acute lesions (rhabdomyolysis, alcoholism, neuroleptic malignant syndrome, toxic drug-induced myopathy, polymyositis) they can often exceed 1000 units and reach up to 40,000.
In progressive muscular dystrophies, these enzymes are increased less, but they are normal in clinically limited chronic forms.2.
Inflammatory muscle diseases are frequent causes of weakness with elevation of CPK levels, as well as aldolase, and they can often be associated with cancers, with autoimmune diseases and with paraneoplastic syndromes, which therefore should be always taken into consideration with a careful anamnestic and laboratory research, but, among the myopathies, idiopathic polymyositis and dermatomyositis are the diseases that most frequently come to the observation of the GP.
However, when serum CK levels are elevated, their assessment over time is an effective help in monitoring the status of the associated disease and of the effectiveness of the therapeutic treatment undertaken.
Dorland’s medical dictionary
2.Principi di neurologia
Adams –Victor 7ed. Mc Graw-Hill
3. Handbook of clinical neurology
Series Editors : Aminoff-Boller-Swaab –vol.63rd.series