Can patent foramen ovale affect rehabilitation? The uncommon association of platypnea-orthodeoxia syndrome and stroke.

Platypnea-orthodeoxia is a rare syndrome characterized by dyspnea and deoxygenation induced by a change to a sitting or standing from a recumbent position. It is the result of posturally accentuated intracardiac or pulmonary right-to-left shunt leading to arterial oxygen desaturation. Only few cases of platypnea-orthodeoxia syndrome are reported in the literature and the association between stroke and platypnea-orthodeoxia syndrome with evidence of patent foramen ovale is extremely rare. We describe the case of a 67-year-old female admitted to our Rehabilitation Unit for disabling basilar stroke due to paradoxical embolism from patent foramen ovale that during the first days of rehabilitation showed signs and symptoms of platypnea-orthodeoxia syndrome. To remove a life-threatening condition for the patient and in order to develop the normal rehabilitation project, that was stopped by the platypnea-orthodeoxia syndrome, the patient fastly underwent to percutaneous closure of patent foramen ovale. The stabilization of oxygen arterial saturation with postural changes and the disappearance of symptoms of POS allowed to develop the rehabilitation project with progressive neurological improvement.

Neuropathies associated with IgG and IgA monoclonal gammopathy.

Neuropathy has been frequently reported in patients with monoclonal gammopathy, particularly those with monoclonal gammopathy of undetermined significance (MGUS). While the neuropathy associated with IgM-MGUS is well characterized and is often associated with a reactivity of the monoclonal protein with neural antigens, the relationship between the neuropathy and IgG and IgA MGUS is less clear. We review here the clinical, electrophysiological and pathogenetic features of neuropathies associated with IgG and IgA M-proteins in order to determine whether they represent distinct clinical entities and, most importantly, whether the finding of an IgG or IgA monoclonal gammopathy in a patient with neuropathy should led to different diagnostic or therapeutical approaches. This review will mainly focus on neuropathies associated with MGUS since the disclosure of a malignant monoclonal gammopathy, including multiple or osteosclerotic myeloma, lymphoma or primary amyloidosis, in a patient with neuropathy usually divert the therapeutical decisions to the hematologist for an appropriate therapy of the underlying life threatening condition.

Long-term prognosis of neuropathy associated with anti-MAG IgM M-proteins and its relationship to immune therapies.

Many data point to a pathogenetic role for IgM antibodies to the myelin-associated glycoprotein (MAG) in the neuropathy associated with IgM monoclonal gammopathy, supporting the use of immune therapies in affected patients. Almost 50% of patients have been reported to improve with these therapies, but the effect of treatment on the long-term prognosis of the neuropathy remains unclear. We analysed the outcome of 25 of the 26 patients (mean age at entry 65 years, range 45-85 years) with neuropathy and high anti-MAG IgM, first examined by us between 1984 and 1994. By January 1999, after a mean follow-up of 8.5 years (range 2-13 years) and a mean duration of neuropathy symptoms of 11.8 years (range 3-18, >10 years in 16), 17 patients (68%) (aged 58-84 years, mean 73.4) were alive, while eight (32%) (aged 69-78 years, mean 73.1) had died 3-15 years (mean 10.6) after neuropathy onset; in none of them was death caused by the neuropathy, although in three it was possibly related to the therapy for the neuropathy. By the time of last follow-up or patients' death, 11 patients (44%) were disabled by severe hand tremor, gait ataxia or both. The disability rates at 5, 10 and 15 years from neuropathy onset were 16, 24 and 50%, respectively. Of the 19 patients treated during the follow-up for 0.5-11 years (mean 4 years) with various immune therapies, five reported a consistent and four a slight improvement in the neuropathy (total 47%) after one treatment or more, but in only one patient was improvement persistent throughout, to the end of follow-up. In 10 patients (53%), severe adverse events, possibly related to therapy, occurred during treatment and were considered responsible for the patient's death in three. The neurological impairment did not differ between treated and untreated patients at the end of a similar follow-up. Our findings indicate that (i) the majority of patients with neuropathy and anti-MAG IgM have a favourable prognosis even after several years, and (ii) current immune therapies, though temporarily effective in half of the patients, are associated with considerable side effects which limit their prolonged use and efficacy, suggesting that until more effective or safer therapies become available, they should probably be reserved for patients impaired in their daily life or in a progressive phase of the disease.

Anti-myelin-associated glycoprotein antibodies predict the development of neuropathy in asymptomatic patients with IgM monoclonal gammopathy.

We examined 52 asymptomatic patients with IgM monoclonal gammopathy and correlated anti-myelin-associated glycoprotein (anti-MAG) IgM with the presence of subclinical neuropathy and, in 24 of these patients, with the development of symptomatic neuropathy during a follow-up interval of 40 to 144 months (mean, 75.3 months). Three of 6 patients (50%) with high (>1/6,400) anti-MAG IgM had subclinical neuropathy at entry compared with 2 of 46 patients (4.3%) with low or no reactivity. At follow-up, a symptomatic neuropathy occurred in 3 of 4 patients with high reactivity and in 3 of 21 patients with low or no reactivity. The correlation of high anti-MAG IgM with the presence of subclinical neuropathy or the development of symptomatic neuropathy supports its pathogenetic role in the neuropathy.

Clinical features and anti-neural reactivity in neuropathy associated with IgG monoclonal gammopathy of undetermined significance.

Neuropathy has been frequently reported in patients with IgG monoclonal gammopathy of undetermined significance (MGUS) but it is still unclear whether this association has clinical or pathogenetic relevance. In order to clarify the possible role of IgG MGUS in the neuropathy we correlated the clinical and electrophysiological features of the neuropathy with the duration and anti-neural activity of the M-protein in 17 patients with neuropathy and IgG MGUS. Ten patients (59%) had a chronic demyelinating neuropathy clinically indistinguishable from chronic inflammatory demyelinating polyneuropathy (CIDP) while 7 (41%) had a predominantly sensory axonal or mixed neuropathy. In 80% of patients in the CIDP-like and 28% in the sensory group the IgG M-protein became manifest several months to years after onset of the neuropathy. Antibodies to one or more neural antigens (including tubulin, a 35KD P0-like nerve myelin glycoprotein, GD1a, GM1 and chondrotin sulfate C) were found in 40% of patients with CIDP-like and 43% with sensory neuropathy but also in 37% patients with IgG MGUS without neuropathy. Neuropathy associated with IgG MGUS is probably less heterogeneous than previously considered suggesting that this association may not be merely casual. The evidence for primary pathogenetic role of IgG M-proteins in the neuropathy remains however elusive.

Spinal reflex pattern to foot nociceptive stimulation in standing humans.

Ipsi- and contralateral patterns of lower limb nociceptive reflex responses were studied in 6 normal subjects in free standing position. Once the position was stabilized, only ankle extensor muscles showed consistent tonic activity while ankle flexors and knee extensors and flexors were virtually silent. Reflex responses, elicited by painful electrical stimuli to the skin of the plantar and dorsal aspect of the foot, were recorded from ipsi- and contralateral quadriceps (Q), biceps femoris (Bic), tibialis anterior (TA) and soleus (Sol) muscles. Plantar foot stimulation evoked a large excitatory response in the ipsilateral TA at about 80 ms and a smaller responses in Bic and Q at 70 ms and 110 ms, respectively. Ipsilateral excitatory effects after dorsal foot stimulation consisted of a Bic response at about 75 ms. In addition to excitatory effects, both plantar and dorsal foot stimulation evoked long-lasting suppression of ipsilateral Sol background activity starting at about 60 ms. Contralaterally, the only nociceptive effects after plantar or dorsal foot stimulation were a small excitatory response of Sol at about 85 ms. Evidence is provided that only excitatory responses were contingent upon nociceptive volley. The main mechanical effects seen after plantar stimulation were dorsiflexion of the foot without loss of heel contact with the floor; no withdrawal response of the foot followed nociceptive dorsal stimulation. Our main conclusion is that only reflex nociceptive responses serving to avoid the stimulus without conflicting with limb support function are expressed. The mechanisms reconciling nociceptive action and postural function of the lower limbs are discussed.